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1. An ethically guided preclinical device for phenotyping H2 production in laboratory rodents

Author

Victor Pascal‐Moussellard, Emilie Boucher, Stéphane Tanguy, Philippe Cinquin, Pierre‐Alain Barraud, Chloé Davin, Cordélia Salomez‐Ihl, Dalil Hannani, François Boucher, and Jean‐Pierre Alcaraz

Subjects
hydrogen therapy, laboratory rodents, microbiota, molecular hydrogen, noninvasive monitoring device, Medicine (General), R5-920
Abstract

Abstract Background Dihydrogen (H2) is produced endogenously by the intestinal microbiota through the fermentation of diet carbohydrates. Over the past few years, numerous studies have demonstrated the significant therapeutic potential of H2 in various pathophysiological contexts, making the characterization of its production in laboratory species of major preclinical importance. Methods This study proposes an innovative solution to accurately monitor H2 production in free‐moving rodents while respecting animal welfare standards. The developed device consisted of a wire rodent cage placed inside an airtight chamber in which the air quality was maintained, and the H2 concentration was continuously analyzed. After the airtightness and efficiency of the systems used to control and maintain air quality in the chamber were checked, tests were carried out on rats and mice with different metabolic phenotypes, over 12 min to 1‐h experiments and repeatedly. H2 production rates (HPR) were obtained using an easy calculation algorithm based on a first‐order moving average. Results HPR in hyperphagic Zucker rats was found to be twice as high as in control Wistar rats, respectively, 2.64 and 1.27 nmol.s−1 per animal. In addition, the ingestion of inulin, a dietary fiber, stimulated H2 production in mice. HPRs were 0.46 nmol.s−1 for animals under control diet and 1.99 nmol.s−1 for animals under inulin diet. Conclusions The proposed device coupled with our algorithm enables fine analysis of the metabolic phenotype of laboratory rats or mice with regard to their endogenous H2 production.

Published
2024
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2. Reflections on Emerging Technologies in Nanomedicine

Author

Munis Dündar, Adam Mechler, Jean-pierre Alcaraz, Gary Henehan, Satya Prakash, Ratnesh Lal, and Donald Martin

Subjects
gene-based biomedicine, antimicrobial peptides, gut microbiota, microbiome, bioinspired technologies, bibliometric analysis., Medicine (General), R5-920
Abstract

Nanomedicine technologies seem to play an increasing role in modern medicine. Although there are many challenges, it is important to consider emerging technologies that may impact nanomedicine. To establish a rational basis for such consideration in this review, we summarise the present state-of-the-art in nanomedicine based on a bibliometric analysis of the literature that is available in the Clarivate® Web of Science. Then, we build upon that state-of-the-art to highlight the emerging technologies that may have an impact on nanomedicine. We also reflect on these emerging technologies by highlighting examples in areas, such as gene-based biomedicine, the rational design of antimicrobial peptides, and diagnosis and therapy of the gut microbiota. In general, emerging technologies that are based on bioinspired and biomimetic approaches appear to provide important pointers to future improvements in nanomedicine.

Published
2020
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3. Controlled Heat and Humidity-Based Treatment for the Reuse of Personal Protective Equipment: A Pragmatic Proof-of-Concept to Address the Mass Shortage of Surgical Masks and N95/FFP2 Respirators and to Prevent the SARS-CoV2 Transmission

Author

Louis Bernard, Guillaume Desoubeaux, Elsa Bodier-Montagutelli, Jeoffrey Pardessus, Déborah Brea, Laurine Allimonnier, Sébastien Eymieux, Pierre-Ivan Raynal, Virginie Vasseur, Laurent Vecellio, Ludovic Mathé, Antoine Guillon, Philippe Lanotte, Jérémie Pourchez, Paul O. Verhoeven, Stéphane Esnouf, Muriel Ferry, Nicolas Eterradossi, Yannick Blanchard, Paul Brown, Philippe Roingeard, Jean-Pierre Alcaraz, Philippe Cinquin, Mustapha Si-Tahar, and Nathalie Heuzé-Vourc'h

Subjects
SARS–CoV-2, facemask, recyclibility, surgical face masks, COVID-19, heating, Medicine (General), R5-920
Abstract

Background: The coronavirus infectious disease-2019 (COVID-19) pandemic has led to an unprecedented shortage of healthcare resources, primarily personal protective equipment like surgical masks, and N95/filtering face piece type 2 (FFP2) respirators.Objective: Reuse of surgical masks and N95/FFP2 respirators may circumvent the supply chain constraints and thus overcome mass shortage. Methods, design, setting, and measurement: Herein, we tested the effects of dry- and moist-air controlled heating treatment on structure and chemical integrity, decontamination yield, and filtration performance of surgical masks and FFP2 respirators.Results: We found that treatment in a climate chamber at 70°C during 1 h with 75% humidity rate was adequate for enabling substantial decontamination of both respiratory viruses, oropharyngeal bacteria, and model animal coronaviuses, while maintaining a satisfying filtering capacity.Limitations: Further studies are now required to confirm the feasibility of the whole process during routine practice.Conclusion: Our findings provide compelling evidence for the recycling of pre-used surgical masks and N95/FFP2 respirators in case of imminent mass shortfall.

Published
2020
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4. Challenges for the Implantation of Symbiotic Nanostructured Medical Devices

Author

Jean-Pierre Alcaraz, Gauthier Menassol, Géraldine Penven, Jacques Thélu, Sarra El Ichi, Abdelkader Zebda, Philippe Cinquin, and Donald K. Martin

Subjects
symbiotic, biocompatibility, bioinspiration, nanobiotechnology, implanted medical device, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

We discuss the perspectives of designing implantable medical devices that have the criterion of being symbiotic. Our starting point was whether the implanted device is intended to have any two-way (“duplex”) communication of energy or materials with the body. Such duplex communication extends the existing concepts of a biomaterial and biocompatibility to include the notion that it is important to consider the intended functional use of the implanted medical device. This demands a biomimetic approach to design functional symbiotic implantable medical devices that can be more efficient in mimicking what is happening at the molecular and cellular levels to create stable interfaces that allow for the unfettered exchanges of molecules between an implanted device and a body. Such a duplex level of communication is considered to be a necessary characteristic of symbiotic implanted medical devices that are designed to function for long periods of time inside the body to restore and assist the function of the body. We illustrate these perspectives with experience gained from implanting functional enzymatic biofuel cells.

Published
2020
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5. Facile bench-top fabrication of enclosed circular microchannels provides 3D confined structure for growth of prostate epithelial cells.

Author

Monika E Dolega, Jayesh Wagh, Sophie Gerbaud, Frederique Kermarrec, Jean-Pierre Alcaraz, Donald K Martin, Xavier Gidrol, and Nathalie Picollet-D'hahan

Subjects
Medicine, Science
Abstract

We present a simple bench-top method to fabricate enclosed circular channels for biological experiments. Fabricating the channels takes less than 2 hours by using glass capillaries of various diameters (from 100 µm up to 400 µm) as a mould in PDMS. The inner surface of microchannels prepared in this way was coated with a thin membrane of either Matrigel or a layer-by-layer polyelectrolyte to control cellular adhesion. The microchannels were then used as scaffolds for 3D-confined epithelial cell culture. To show that our device can be used with several epithelial cell types from exocrine glandular tissues, we performed our biological studies on adherent epithelial prostate cells (non-malignant RWPE-1 and invasive PC3) and also on breast (non-malignant MCF10A) cells We observed that in static conditions cells adhere and proliferate to form a confluent layer in channels of 150 µm in diameter and larger, whereas cellular viability decreases with decreasing diameter of the channel. Matrigel and PSS (poly (sodium 4-styrenesulphonate)) promote cell adhesion, whereas the cell proliferation rate was reduced on the PAH (poly (allylamine hydrochloride))-terminated surface. Moreover infusing channels with a continuous flow did not induce any cellular detachment. Our system is designed to simply grow cells in a microchannel structure and could be easily fabricated in any biological laboratory. It offers opportunities to grow epithelial cells that support the formation of a light. This system could be eventually used, for example, to collect cellular secretions, or study cell responses to graduated hypoxia conditions, to chemicals (drugs, siRNA, …) and/or physiological shear stress.

Published
2014
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6. A glucose biofuel cell implanted in rats.

Author

Philippe Cinquin, Chantal Gondran, Fabien Giroud, Simon Mazabrard, Aymeric Pellissier, François Boucher, Jean-Pierre Alcaraz, Karine Gorgy, François Lenouvel, Stéphane Mathé, Paolo Porcu, and Serge Cosnier

Subjects
Medicine, Science
Abstract

Powering future generations of implanted medical devices will require cumbersome transcutaneous energy transfer or harvesting energy from the human body. No functional solution that harvests power from the body is currently available, despite attempts to use the Seebeck thermoelectric effect, vibrations or body movements. Glucose fuel cells appear more promising, since they produce electrical energy from glucose and dioxygen, two substrates present in physiological fluids. The most powerful ones, Glucose BioFuel Cells (GBFCs), are based on enzymes electrically wired by redox mediators. However, GBFCs cannot be implanted in animals, mainly because the enzymes they rely on either require low pH or are inhibited by chloride or urate anions, present in the Extra Cellular Fluid (ECF). Here we present the first functional implantable GBFC, working in the retroperitoneal space of freely moving rats. The breakthrough relies on the design of a new family of GBFCs, characterized by an innovative and simple mechanical confinement of various enzymes and redox mediators: enzymes are no longer covalently bound to the surface of the electron collectors, which enables use of a wide variety of enzymes and redox mediators, augments the quantity of active enzymes, and simplifies GBFC construction. Our most efficient GBFC was based on composite graphite discs containing glucose oxidase and ubiquinone at the anode, polyphenol oxidase (PPO) and quinone at the cathode. PPO reduces dioxygen into water, at pH 7 and in the presence of chloride ions and urates at physiological concentrations. This GBFC, with electrodes of 0.133 mL, produced a peak specific power of 24.4 microW mL(-1), which is better than pacemakers' requirements and paves the way for the development of a new generation of implantable artificial organs, covering a wide range of medical applications.

Published
2010
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7. Improved micro-impedance spectroscopy to determine cell barrier properties

Author

Md. Mehadi Hasan Sohag, Abir Khalil-Mgharbel, Isabelle Vilgrain, Jean-Pierre Alcaraz, Racha Amine, Donald K. Martin, and Olivier Nicoud

Subjects
renal proximal tubule epithelial cell, Materials science, Biomedical Engineering, Nanotechnology, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, electrical impedance spectroscopy, 0104 chemical sciences, Dielectric spectroscopy, cancerous kidney cell, Genetics, Molecular Medicine, cell monolayer, 0210 nano-technology, Molecular Biology, TP248.13-248.65, Food Science, Biotechnology
Abstract

The goal of this study was to determine whether the Tethapod system, which was designed to determine the impedance properties of lipid bilayers, could be used for cell culture in order to utilise micro-impedance spectroscopy to examine further biological applications. To that purpose we have used normal epithelial cells from kidney (RPTEC) and a kidney cancer cell model (786-O). We demonstrate that the Tethapod system is compatible with the culture of 10,000 cells seeded to grow on a small area gold measurement electrode for several days without affecting the cell viability. Furthermore, the range of frequencies for EIS measurements were tuned to examine easily the characteristics of the cell monolayer. We demonstrate significant differences in the paracellular resistance pathway between normal and cancer kidney epithelial cells. Thus, we conclude that this device has advantages for the study of cultured cells that include (i) the configuration of measurement and reference electrodes across a microfluidic channel, and (ii) the small surface area of 6 parallel measurement electrodes (2.1 mm2) integrated in a microfluidic system. These characteristics might improve micro-impedance spectroscopy measurement techniques to provide a simple tool for further studies in the field of the patho-physiology of biological barriers.

Published
2020

8. Supercritical carbon dioxide-based cleaning and sterilization treatments for the reuse of filtering facepiece respirators FFP2 in the context of COVID-19 pandemic

Author

Guillaume Aubert, N. Jidenko, Victor Mocho, Philippe Cinquin, Soleiman Bourrous, Cyril Aymonier, Mathieu Barrault, François-Xavier Ouf, Samuel Marre, Jean-Pierre Alcaraz, Anaïs Cario, Jean-Pascal Borra, Institut de Chimie de la Matière Condensée de Bordeaux (ICMCB), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Laboratoire de physique des gaz et des plasmas (LPGP), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), The authors thank Paul Boyé and Kolmi, who kindly procured the FFP2s on which this protocol was developed. This work is part of a French task-force initiated by CNRS and CEA, involving several research organisms and industrial partners. We thank Pr. Roger Salamon, who helped procure the first FFP2s on which the SCCD protocol was developed. We also thank the European Research Council., Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-SyNaBi ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), and Centre Hospitalier Universitaire [Grenoble] (CHU)

Subjects
business.product_category, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, 020209 energy, General Chemical Engineering, cleaning, Context (language use), 02 engineering and technology, 010501 environmental sciences, Reuse, 01 natural sciences, 12. Responsible consumption, law.invention, supercritical CO2, law, 0202 electrical engineering, electronic engineering, information engineering, Physical and Theoretical Chemistry, Respirator, Filtration, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, Supercritical carbon dioxide, filtering performances, Waste management, FFP2 face protective equipment, sterilization, Human decontamination, [CHIM.MATE]Chemical Sciences/Material chemistry, Sterilization (microbiology), Condensed Matter Physics, Supercritical fluid, 13. Climate action, Environmental science, business
Abstract

International audience; Supercritical Carbon Dioxide treatment of clean and soiled Filtering Face-Piece respirators is shown to meet mandatory requirements for safe reuse of FFP2. Preliminary tests enabled us to select optimal conditions for Supercritical Carbon Dioxide treatment of FFP2, for one hour at 343 K under 7.5 MPa, with a biocide solution. FFP2s from Paul Boyé ® were then tested before and after Supercritical Carbon Dioxide treatment with a soiling solution and a biological indicator (i.e. spores of GeoBacillus stearothermophilus) with respect to three objectives: (i) washing of organic deposits, (ii) sterilization (i.e. spores inactivation) and (iii) preservation of the filtration performances. The proposed Supercritical Carbon Dioxide treatment fulfils these three criterions, with effective decontamination of spores and promising washing preserving FFP2 requirements for filtration efficiency of aerosol (> 94%) with acceptable pressure drop (< 240 Pa). As a simple and low-cost one-step recycling method, Supercritical Carbon Dioxide fits to economical and sustainable development standpoints but also allows one to come back to good practices of face protective equipment use, lowering eventual shortage and tensions for most countries importing these respirators.

Published
2022

9. Nanostructural Characterization of Cardiolipin-Containing Tethered Lipid Bilayers Adsorbed on Gold and Silicon Substrates for Protein Incorporation

Author

Jean-Pierre Alcaraz, Donald K. Martin, Andrew Nelson, Giovanna Fragneto, Marco Maccarini, Sebastian Köhler, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-SyNaBi ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), and Université Grenoble Alpes (UGA)

Subjects
Silicon, Cardiolipins, Lipid Bilayers, 02 engineering and technology, 03 medical and health sciences, chemistry.chemical_compound, Electrochemistry, Cardiolipin, Molecule, General Materials Science, Lipid bilayer, Spectroscopy, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, Bilayer, Surfaces and Interfaces, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Nanostructures, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Membrane, chemistry, Membrane protein, Biophysics, lipids (amino acids, peptides, and proteins), Gold, Neutron reflectometry, 0210 nano-technology, Ethylene glycol
Abstract

A key to the development of lipid membrane-based devices is a fundamental understanding of how the molecular structure of the lipid bilayer membrane is influenced by the type of lipids used to build the membrane. This is particularly important when membrane proteins are included in these devices since the precise lipid environment affects the ability to incorporate membrane proteins and their functionality. Here, we used neutron reflectometry to investigate the structure of tethered bilayer lipid membranes and to characterize the incorporation of the NhaA sodium proton exchanger in the bilayer. The lipid membranes were composed of two lipids, dioleoyl phosphatidylcholine and cardiolipin, and were adsorbed on gold and silicon substrates using two different tethering architectures based on functionalized oligoethylene glycol molecules of different lengths. In all of the investigated samples, the addition of cardiolipin caused distinct structural rearrangement including crowding of ethylene glycol groups of the tethering molecules in the inner head region and a thinning of the lipid tail region. The incorporation of NhaA in the tethered bilayers following two different protocols is quantified, and the way protein incorporation modulates the structural properties of these membranes is detailed.

Published
2021

10. Challenges for the Implantation of Symbiotic Nanostructured Medical Devices

Author

Jacques Thélu, Philippe Cinquin, Sarra El Ichi, Donald K. Martin, Abdelkader Zebda, Jean-Pierre Alcaraz, Geraldine Penven, Gauthier Menassol, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Neurodegenerescence et Plasticite, and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Medical device, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Biocompatibility, Computer science, Duplex (telecommunications), 02 engineering and technology, 010402 general chemistry, 01 natural sciences, nanobiotechnology, lcsh:Technology, lcsh:Chemistry, biocompatibility, Human–computer interaction, General Materials Science, Instrumentation, lcsh:QH301-705.5, Implanted device, ComputingMilieux_MISCELLANEOUS, Fluid Flow and Transfer Processes, lcsh:T, Process Chemistry and Technology, General Engineering, 021001 nanoscience & nanotechnology, lcsh:QC1-999, 0104 chemical sciences, Computer Science Applications, lcsh:Biology (General), lcsh:QD1-999, bioinspiration, lcsh:TA1-2040, symbiotic, Bioinspiration, 0210 nano-technology, lcsh:Engineering (General). Civil engineering (General), Biofuel Cells, lcsh:Physics, implanted medical device
Abstract

We discuss the perspectives of designing implantable medical devices that have the criterion of being symbiotic. Our starting point was whether the implanted device is intended to have any two-way (“duplex”) communication of energy or materials with the body. Such duplex communication extends the existing concepts of a biomaterial and biocompatibility to include the notion that it is important to consider the intended functional use of the implanted medical device. This demands a biomimetic approach to design functional symbiotic implantable medical devices that can be more efficient in mimicking what is happening at the molecular and cellular levels to create stable interfaces that allow for the unfettered exchanges of molecules between an implanted device and a body. Such a duplex level of communication is considered to be a necessary characteristic of symbiotic implanted medical devices that are designed to function for long periods of time inside the body to restore and assist the function of the body. We illustrate these perspectives with experience gained from implanting functional enzymatic biofuel cells.

Published
2020

11. The biocompatibility of biofuel cells operating inside the body

Author

Abdelkader Zebda, Geraldine Penven, Gauthier Menassol, Jacques Thélu, Sarra El Ichi, François Boucher, Lionel Dubois, Jean-Pierre Alcaraz, Donald K. Martin, Philippe Cinquin, Alcaraz, Jean-Pierre, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-PRETA ), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), Neurodégénérescence et Plasticité, [GIN] Grenoble Institut des Neurosciences (GIN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Conception d’Architectures Moléculaires et Processus Electroniques (CAMPE ), SYstèmes Moléculaires et nanoMatériaux pour l’Energie et la Santé (SYMMES), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA), Département Interfaces pour l'énergie, la Santé et l'Environnement (DIESE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), and Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-IMAG-PRETA)

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Materials science, Biocompatibility, Bioelectric Energy Sources, Nanotechnology, Biocompatible Materials, 02 engineering and technology, Electrolyte, 010402 general chemistry, 7. Clean energy, 01 natural sciences, Biochemistry, Catalysis, Electrolytes, Mice, 3T3-L1 Cells, Electrochemistry, Animals, Electrodes, ComputingMilieux_MISCELLANEOUS, Power density, Chitosan, Bacteria, 021001 nanoscience & nanotechnology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 0104 chemical sciences, Nanostructures, Glucose, Energy density, Fuel cells, Current (fluid), 0210 nano-technology, Biofuel Cells
Abstract

In 1968 Wolfson et al. published the concept for producing energy inside the body using catalytic electrodes exposed to the body fluid as an electrolyte and utilising naturally occurring fuels such as glucose. Since then, the technology has advanced to enhance the levels of power using enzymes immobilised within three-dimensional bioelectrodes that are nanostructured. Current research in the field of enzymatic fuel cells is directed toward applying electrochemical and nanostructural expertise to increase the energy density, to increase the power density, to increase the operational stability, and to increase the voltage output. Nonetheless, biocompatibility remains the major challenge for increasing the life-time for implanted enzymatic biofuel cells. Here, we discuss the current issues for biocompatibility and suggest directions to enhance the design of biofuel cells so as to increase the life-time of implantation whilst maintaining sufficient performance to provide power for implanted medical devices.

Published
2020

12. Reflections on Emerging Technologies in Nanomedicine

Author

Donald K. Martin, Gary T. M. Henehan, Adam Mechler, Ratnesh Lal, Jean-Pierre Alcaraz, Satya Prakash, Munis Dundar, Medicine Faculty, Erciyes University, School of Chemistry, Monash UniVersity, Clayton, VIC. 3800 (Australia), Monash University [Clayton], Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Technological University [Dublin] (TU), University of California [San Diego] (UC San Diego), University of California, and Biomedical Technology and Cell Therapy Research Laboratory, Montreal

Subjects
0106 biological sciences, Modern medicine, Bibliometric analysis, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Web of science, Emerging technologies, microbiome, 01 natural sciences, bibliometric analysis, antimicrobial peptides, 03 medical and health sciences, Medicine, Biomedicine, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, lcsh:R5-920, 0303 health sciences, bioinspired technologies, gut microbiota, business.industry, gene-based biomedicine, 3. Good health, Nanomedicine, Engineering ethics, lcsh:Medicine (General), business, 010606 plant biology & botany
Abstract

Nanomedicine technologies seem to play an increasing role in modern medicine. Although there are many challenges, it is important to consider emerging technologies that may impact nanomedicine. To establish a rational basis for such consideration in this review, we summarise the present state-of-the-art in nanomedicine based on a bibliometric analysis of the literature that is available in the Clarivate (R) Web of Science. Then, we build upon that state-of-the-art to highlight the emerging technologies that may have an impact on nanomedicine. We also reflect on these emerging technologies by highlighting examples in areas, such as gene-based biomedicine, the rational design of antimicrobial peptides, and diagnosis and therapy of the gut microbiota. In general, emerging technologies that are based on bioinspired and biomimetic approaches appear to provide important pointers to future improvements in nanomedicine.

Published
2020

13. Remote wireless control of an enzymatic biofuel cell implanted in a rabbit for 2 months

Author

Bertrand Boutaud, Jean Pierre Alcaraz, Renzo Dalmolin, Donald K. Martin, François Boucher, Sarra El Ichi-Ribault, Abdelkader Zebda, Philippe Cinquin, Jean Boutonnat, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-IMAG-PRETA), Sorin Group [Clamart], and Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx)

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Chemistry, General Chemical Engineering, 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, Biocompatible material, 01 natural sciences, 0104 chemical sciences, Bioelectrochemistry, Electrochemistry, Biocompatibility, Rabbit implantation, Power output, Wireless recording and control, Enzymatic biofuel cell, 0210 nano-technology, Charge and discharge, Biofuel Cells, Biomedical engineering, Wireless control
Abstract

International audience; A bioelectronic device comprising an enzymatic biofuel cell (GBFC) connected to a wireless tele-transmission system was implanted in a rabbit and its function was monitored and controlled in vivo for a period of 2 months. After the 18th day of implantation, the tele-transmission system was used to wirelessly charge and discharge the operational GBFC in vivo through a 100 kU load for 30 min each day. For a further 16 days of operation, the GBFC delivered 16 mW mL À1 continuously during each 30 min discharge each day for 16 days. At the end of the 2 month period of implantation the power output had diminished, which was most likely due to an inflammatory process. Our results also indicate that the duration of operational activity is increased by optimizing the interface between the GBFC and the body to minimize inflammatory processes and biofouling. These data provide a significant advance in the achievable output from a GBFC that is implanted in a mammal, and importantly provide a basis upon which to further develop stable implantable biofuel cells. Improving the in vivo performance of an implanted GBFC includes the development of biocompatible diffusing polymers to act as buffering diffusion barriers.

Published
2018

14. Functional Characterization of Cell-Free Expressed OprF Porin from Pseudomonas aeruginosa Stably Incorporated in Tethered Lipid Bilayers

Author

Landry Gayet, Lavinia Liguori, Jean-Pierre Alcaraz, Jean-Luc Lenormand, Erik B. Watkins, Marco Maccarini, Barry Stidder, Donald K. Martin, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Los Alamos National Laboratory (LANL), and Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx)

Subjects
0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Protein Conformation, Lipid Bilayers, Porins, Virulence, medicine.disease_cause, Biophysical Phenomena, law.invention, 03 medical and health sciences, law, Electrochemistry, medicine, General Materials Science, Lipid bilayer, ComputingMilieux_MISCELLANEOUS, Spectroscopy, biology, Chemistry, Pseudomonas aeruginosa, Surfaces and Interfaces, Condensed Matter Physics, biology.organism_classification, 030104 developmental biology, Biochemistry, Porin, Recombinant DNA, Neutron reflectometry, Function (biology), Bacteria
Abstract

OprF has a central role in Pseudomonas aeruginosa virulence and thus provides a putative target for either vaccines or antibiotic cofactors that could overcome the bacterium's natural resistance to antibiotics. Here we describe a procedure to optimize the production of highly pure and functional OprF porins that are then incorporated into a tethered lipid bilayer. This is a stable biomimetic system that provides the capability to investigate structural aspects and function of OprF using and neutron reflectometry and electrical impedance spectroscopy. The recombinant OprF produced using the optimized cell-free procedure yielded a quantity of between 0.5 to 1.0 mg/mL with a purity ranging from 85 to 91% in the proteoliposomes. The recombinant OprF is capable of binding IFN-γ and is correctly folded in the proteoliposomes. Because OprF proteins form pores the biomimetic system allowed the measurement of OprF conductance using impedance spectroscopy. The neutron reflectometry measurements showed that the OprF protein is incorporated into the lipid bilayer but with parts of the protein in both the regions above and below the lipid bilayer. Those structural aspects are coherent with the current assumed structure of a transmembrane N-terminal domain composed by eight stranded beta-barrels and a globular C-terminal domain located in the periplasm. Currently there are no crystal structures available for OprF. The experimental model system that we describe provides a basis for further fundamental studies of OprF and particularly for the ongoing biotechnological development of OprF as a target for antibacterial drugs.

Published
2017

15. A PANI supported lipid bilayer that contains NhaA transporter proteins provides a basis for a biomimetic biocapacitor

Author

Landry Gayet, Abderrahim Boualam, Awatef Ben Tahar, Philippe Cinquin, Jean-Pierre Alcaraz, Abdelkader Zebda, Donald K. Martin, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO)

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Biomimetic membranes, Sodium-Hydrogen Exchangers, Lipid Bilayers, Biosensing Techniques, 010402 general chemistry, 01 natural sciences, Catalysis, chemistry.chemical_compound, Biomimetic Materials, Polyaniline, Materials Chemistry, Lipid bilayer, Electrodes, ComputingMilieux_MISCELLANEOUS, Ion transporter, High turnover, Aniline Compounds, 010405 organic chemistry, Escherichia coli Proteins, Metals and Alloys, Transporter, General Chemistry, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Membrane, chemistry, Dielectric Spectroscopy, Ceramics and Composites, Biophysics, Gold
Abstract

We designed a supported lipid bilayer (SLB) biomimetic membrane system that comprised polyaniline (PANI) to support a lipid bilayer membrane that incorporated Na+/H+ transporter proteins (NhaA) to give the system the capability of controllable electrogenic ion transport. The high turnover rate of NhaA (∼105 per min) provides the basis for this PANI-SLB-NhaA system to be a high-speed rechargeable biocapacitor that functions as a low-energy-consuming fast switch for biological engineering applications.

Published
2019

16. Challenges for successful implantation of biofuel cells

Author

Pankaj Vadgama, Abdelkader Zebda, Sergey Shleev, Donald K. Martin, Jean-Pierre Alcaraz, Shelley D. Minteer, François Boucher, Philippe Cinquin, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), sans affiliation, Biomedical Laboratory Science, Malmö University, Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-IMAG-PRETA), and Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO)

Subjects
Engineering, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Biocompatibility, Bioelectric Energy Sources, Biophysics, Biocompatible Materials, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Living body, complex mixtures, Long-term power output, Naturvetenskap, Electrochemistry, Animals, Physical and Theoretical Chemistry, Electrodes, Ethics, business.industry, fungi, technology, industry, and agriculture, food and beverages, Electrochemical Techniques, General Medicine, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Biofuel, Implanted biofuel cell, Biochemical engineering, 0210 nano-technology, business, Natural Sciences, Biofuel Cells
Abstract

There is a growing interest in the design and engineering of operational biofuel cells that can be implanted. This review highlights the recent progress in the electrochemistry of biofuel cell technologies, but with a particular emphasis on the medical and physiological aspects that impact the biocompatibility of biofuel cells operating inside a living body. We discuss the challenge of supplying power to implantable medical devices, with regard to the limitations of lithium battery technology and why implantable biofuel cells can be a promising alternative to provide the levels of power required for medical devices. In addition to the challenge of designing a biofuel cell that provides a stable level of sufficient power, the review highlights the biocompatibility and biofouling problems of implanting a biofuel cell that have a major impact on the availability of the substrates inside body that provide fuel for the biofuel cell. These physiological challenges and associated ethical considerations are essential to consider for biofuel cells that are designed to be implanted for long-term operation inside a living animal and eventually to human clinical applications. (C) 2018 The Authors. Published by Elsevier B.V.

Published
2018

17. Cell-free production of VDAC directly into liposomes for integration with biomimetic membrane systems

Author

Jean-Luc Lenormand, Lavinia Liguori, Donald K. Martin, Jean-Pierre Alcaraz, Philippe Cinquin, Barry Stidder, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx)

Subjects
0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Voltage-dependent anion channel, Mitochondrial intermembrane space, Blotting, Western, membrane proteins, Nanotechnology, Biochemistry, Transport Pathway, VDAC liposomes, 03 medical and health sciences, 0302 clinical medicine, Biomimetics, Voltage-Dependent Anion Channels, cell-free expression system, Cloning, Molecular, Microscopy, Immunoelectron, Liposome, Cell-Free System, Biomimetic devices, biology, Chemistry, Circular Dichroism, Membranes, Artificial, General Medicine, electrical measurements, Transport protein, Cytosol, 030104 developmental biology, Membrane protein, Liposomes, Biomimetic Devices, biology.protein, Biophysics, 030217 neurology & neurosurgery, Biotechnology
Abstract

International audience; The mitochondrial voltage-dependent anion channel (VDAC) is a pivotal protein since it provides the major transport pathway between the cytosol and the mitochondrial intermembrane space and it is implicated in cell apoptosis by functioning as a gatekeeper for the trafficking of mitochondrial death molecules. VDAC is a beta-barrel channel with a large conductance, and we use it as a model transport protein for the design of biomimetic systems. To overcome the limitations of classical overexpression methods for producing and purifying membrane proteins (MPs) we describe here the use of an optimized cell-free system. In a one-step reaction VDAC is obtained directly integrated into liposomes and purified by ultracentrifugation. We then combine proteoliposomes with different bilayers models in order to validate VDAC insertion and functionality. This VDAC biomimetic model is the first example validating the use of a cell-free expression system for production of MPs into liposomes and tethered bilayers as a toolbox to build a wide range of biomimetic devices.

Published
2016

18. Long duration stabilization of porous silicon membranes in physiological media: Application for implantable reactors

Author

Frederic Gaillard, Donald K. Martin, Chantal Gondran, Marie-Line Cosnier, Guillaume Nonglaton, Philippe Cinquin, Jean-Pierre Alcaraz, Guillaume Costa, Abdoullatif Baraket, Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Département de Chimie Moléculaire - Biosystèmes Electrochimiques et Analytiques (DCM - BEA ), Département de Chimie Moléculaire (DCM), Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-GMCAO), Translational Innovation in Medicine and Complexity / Recherche Translationnelle et Innovation en Médecine et Complexité - UMR 5525 (TIMC ), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Gestes Médico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), and ANR-17-EURE-0003,CBH-EUR-GS,CBH-EUR-GS(2017)

Subjects
Silicon, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Time Factors, Materials science, Diffusion, Bioengineering, 02 engineering and technology, 010402 general chemistry, Porous silicon, 01 natural sciences, Fluorescence, law.invention, Biomaterials, Bioreactors, law, Immersion (virtual reality), ComputingMilieux_MISCELLANEOUS, Filtration, chemistry.chemical_classification, Escherichia coli Proteins, Biomolecule, Membranes, Artificial, Prostheses and Implants, Silanes, 021001 nanoscience & nanotechnology, Culture Media, 0104 chemical sciences, Glucose, Membrane, chemistry, Chemical engineering, Mechanics of Materials, PEGylation, Nanoparticles, Surface modification, Fluorescein, 0210 nano-technology, Porosity
Abstract

The natural biodegradabilty of porous silicon (pSi) in physiological media limits its wider usage for implantable systems. We report the stabilization of porous silicon (pSi) membranes by chemical surface oxidation using RCA1 and RCA2 protocols, which was followed by a PEGylation process using a silane-PEG. These surface modifications stabilized the pSi to allow a long period of immersion in PBS, while leaving the pSi surface sufficiently hydrophilic for good filtration and diffusion of several biomolecules of different sizes without any blockage of the pSi structure. The pore sizes of the pSi membranes were between 5 and 20 nm, with the membrane thickness around 70 μm. The diffusion coefficient for fluorescein through the membrane was 2 × 10−10 cm2 s−1, and for glucose was 2.2 × 10−9 cm2 s−1. The pSi membrane maintained that level of glucose diffusion for one month of immersion in PBS. After 2 months immersion in PBS the pSi membrane continued to operate, but with a reduced glucose diffusion coefficient. The chemical stabilization of pSi membranes provided almost 1 week stable and functional biomolecule transport in blood plasma and opens the possibility for its short-term implantation as a diffusion membrane in biocompatible systems.

Published
2020

19. A Biomimetic Lipid Membrane Device Reveals the Interaction of Cancer Biomarkers with Human Serum Lipidic Moieties

Author

Abir Khalil-Mgharbel, Paul K. Dembélé, Isabelle Vilgrain, Jean-Pierre Alcaraz, Md. Mehadi Hasan Sohag, Donald K. Martin, Helena Polena, Laboratoire de développement et vieillissement de l'endothélium, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), and Alcaraz, Jean-Pierre

Subjects
0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Lipoproteins, [SPI.NANO] Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, [SDV]Life Sciences [q-bio], Population, [SDV.CAN]Life Sciences [q-bio]/Cancer, Applied Microbiology and Biotechnology, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Antigens, CD, Biomimetic Materials, Biomarkers, Tumor, medicine, Humans, Immunoprecipitation, Nanotechnology, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, education, Lipid bilayer, ComputingMilieux_MISCELLANEOUS, education.field_of_study, Apolipoprotein A-I, biology, Chemistry, Cancer, General Medicine, Models, Theoretical, Cadherins, medicine.disease, Kidney Neoplasms, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 3. Good health, [SDV] Life Sciences [q-bio], Cholesterol, HEK293 Cells, 030104 developmental biology, Biochemistry, 030220 oncology & carcinogenesis, biology.protein, Molecular Medicine, Biomarker (medicine), lipids (amino acids, peptides, and proteins), Apolipoprotein A1, Cancer biomarkers, Ultracentrifuge, Biotechnology, Lipoprotein
Abstract

A major problem for the detection of cancer biomarkers in plasma or serum is that common clinical practice does not require the patient to be in a fasting state. Considering that lipoproteins are the main population affected by food intake, the authors hypothesized that biomarkers could be embedded in lipid particles and thereby opens a new avenue for detection. Using the recently published biomarker, soluble VE-cadherin (sVE), the authors tested our hypothesis using techniques of biophysics, biochemistry and the tools of nanobiotechnology on serum samples from kidney cancer patients (n = 106). Optical density as well as contact angle measurements of serum revealed heterogeneity in the particle content of the serum samples. Isolation of the lipidic moieties by ultracentrifugation showed that sVE was detected in this compartment. Further, isolation of lipoprotein subclasses by precipitation with sodium phosphotungstate and MgCl2 , showed that HDL carried the majority of sVE. Immunoprecipitation of sVE confirmed that it was associated with Apolipoprotein A1, a major compound of HDL. Using a biomimetic lipid bilayer membrane coupled with impedance spectroscopy the authors quantified, in real-time, that the sVE adsorbed to the lipid bilayer membrane without altering its structure. Taken together, these results show for the first time a direct interaction of a cancer biomarker with lipids. The authors anticipate these results to prompt fasting for future blood tests for large-scale studies in the biomarkers research field.

Published
2018

21. 3D polyelectrolyte scaffolds to mimic exocrine glands: a step towards a prostate-on-chip platform

Author

Odile Filhol-Cochet, Frédérique Kermarrec, Maxime Legues, Xavier Gidrol, Guillaume Laffitte, Christophe A. Marquette, Jean-Pierre Alcaraz, Olivier Nicoud, Nathalie Picollet-D'hahan, Florence Rivera, Isabelle Vilgrain, Lavinia Liguori, Jacques Thélu, Patricia Obeid, Donald K. Martin, Ali Bouamrani, Sophie Gerbaud, Benoit Gilquin, Thibaud Moufle-Milot, Adrien Mombrun, Cristina Belda Marin, Axel Tollance, Biomicrotechnologie et génomique fonctionnelle (BIOMICS), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Génie Enzymatique, Membrane Biomimétique et Assemblages Supramoléculaires (GEMBAS), Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (ICBMS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-École Supérieure Chimie Physique Électronique de Lyon-Centre National de la Recherche Scientifique (CNRS), Invasion mechanisms in angiogenesis and cancer (IMAC), Biologie du Cancer et de l'Infection (BCI ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut National de la Santé et de la Recherche Médicale (INSERM), Commissariat à l'énergie atomique et aux énergies alternatives - Laboratoire d'Electronique et de Technologie de l'Information (CEA-LETI), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Clinatec - Centre de recherche biomédicale Edmond J.Safra (SCLIN), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université de Lyon-Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Exocrine gland, 3D scaffolds, Biomedical Engineering, Nanotechnology, polyelectrolytes, 03 medical and health sciences, 0302 clinical medicine, Prostate, Genetics, medicine, Liquid biopsy, [SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, liquid biopsy, Polyelectrolyte, secretome, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Molecular Medicine, organ-on-chip, TP248.13-248.65, Food Science, Biotechnology
Abstract

We report our approach to creating a microfluidic chip (namely UroLOC) that mimics the acinar/tubular structure and the luminal microenvironment of exocrine glands. The chip utilises a nanostructured membrane that is designed to provide a 3-dimensional supporting scaffold for the growth of exocrine acinus epithelial cells. The nanostructured membrane was produced using layer-by-layer assembly of polyelectrolytes, and formed into 3-dimensional hemispherical cavities and “finger-like” structures in order to mimic the natural architecture of acini found in exocrine glands. We utilised normal (PNT2) and cancerous (PC3, LNCaP) prostate epithelial cells to demonstrate the proof-of-concept of using MALDI (Matrix Assisted Laser Desorption Ionisation) profiling of secretions collected after 48 hours of cell growth, with no concentration or purification steps and without any a priori on the knowledge of targeted proteins. This MALDI profiling analysis of the crude supernatants from 3 different cell lines (PNT2, PC3 and LNCaP) demonstrated the capacity of the MALDI profiling approach to discriminate between the different secretome signatures. The UroLOC concept and secretome profiling that we describe opens new opportunities in terms of liquid-biopsy based diagnosis, particularly for the early stages of carcinogenesis.

Published
2018

22. Building on biomimetics: Nanotechnology and novel medical devices

Author

Jean Pierre Alcaraz, Abdelkader Zebda, Faezeh Gerayeli, Awatef Ben Tahar, Marco Maccarini, Donald K. Martin, Jacques Thélu, Gauthier Menassol, Sebastien Koehler, Philippe Cinquin, Thomas Soranzo, and Pierre Harispuru

Subjects
Engineering, business.industry, Bioengineering, Nanotechnology, General Medicine, Biomimetics, business, Applied Microbiology and Biotechnology, Biotechnology
Published
2018

23. The modulation of attachment, growth and morphology of cancerous prostate cells by polyelectrolyte nanofilms

Author

Xavier Gidrol, Ricky Bhajun, Philippe Cinquin, Nathalie Picollet-D'hahan, Eric Sulpice, Jean-Pierre Alcaraz, Frédérique Kermarrec, Jayesh Wagh, Donald K. Martin, Sophie Gerbaud, Patricia Obeid, Laurent Guyon, Monika E. Dolega, Laboratoire Biopuces (BIOPUCES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Laboratoire de Biologie à Grande Échelle (BGE - UMR S1038), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Structures et propriétés d'architectures moléculaire (SPRAM - UMR 5819), Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Biosciences et de Biotechnologies de Grenoble (ex-IRTSV) (BIG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes (UGA)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes (UGA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Institut Nanosciences et Cryogénie (INAC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])

Subjects
Male, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Materials science, Polymers, Carcinogenesis, Biophysics, Bioengineering, Epithelial cells, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Cell Line, Allylamine, Focal adhesion, Biomaterials, chemistry.chemical_compound, Animals, Cytotoxic T cell, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Cell adhesion, Cell proliferation, biology, Cell growth, Prostate, Prostatic Neoplasms, Adhesion, Models, Theoretical, Layer-by-layer, 021001 nanoscience & nanotechnology, Polyelectrolytes, Rats, 0104 chemical sciences, Fibronectin, chemistry, Cell culture, Mechanics of Materials, Immunology, biology.protein, Ceramics and Composites, 0210 nano-technology
Abstract

free download pdf : http://ac.els-cdn.com/S0142961213010715/1-s2.0-S0142961213010715-main.pdf?_tid=af9b5ff8-4bae-11e3-b1b0-00000aab0f27&acdnat=1384270119_77de34b330a3942315169996314d8ce3; International audience; The behaviour of cancerous epithelial prostatic cells (PC3) growing on polyelectrolytes (PE) coatings was compared to the behaviour of immortalized normal prostatic cells (PNT-2). The cell behaviour was evaluated and quantified in terms of initial cell attachment, growth, metabolic activity, morphometry, adhesion, apoptosis and stress related gene expression. Both the anionic PSS (poly(sodium 4-styrenesulphonate))-terminated surface and cationic PAH (poly(allylamine hydrochloride))-terminated surfaces were not cytotoxic. The initial attachment of cells was better on the PAH-terminated surface compared to fibronectin. However, the proliferation rate of PC3 cells was reduced on the PAH-terminated surface and slightly increased on the PSS coatings. Only PAH prevented the clustering phenotype of PC3 and reduced the number of focal adhesion points as compared to fibronectin or PSS coatings. In contrast, none of the PE surfaces significantly affected the biological responses of PNT-2 cells. PAH-terminating films provide a tool to preferentially modulate the growth of some cancerous phenotypes, in this case as a micro-environment that reduces the growth of metastatic PC3 cells.

Published
2013
Full Text
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24. Réacteur intestinal implantable

Author

Philippe Cinquin, Dominique Schneider, Max Maurin, Donald Martin, Sarra El Ichi, Abdelkader Zebda, jean-pierre alcaraz, Fabian Reche, Patrick Tuvignon, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Génomique et Évolution des Microorganismes (TIMC-IMAG-GEM), Centre Hospitalier Universitaire [Grenoble] (CHU), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), and Alcaraz, Jean-Pierre

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology
Published
2016

25. [Shades of grays for implanting an enzymatic biofuel cell]

Author

Jean-Pierre, Alcaraz, Sarra El, Ichi-Ribault, Laurent, Cortella, Catherine, Guimier-Pingault, Abdelkader, Zebda, Philippe, Cinquin, and Donald K, Martin

Subjects
Oxygen, Glucose Oxidase, Glucose, Bioelectric Energy Sources, Laccase, Animals, Humans, Biosensing Techniques, Enzymes, Immobilized, Electrodes, Implanted
Abstract

An implanted biofuel cell (IBFC) is a novel device that provides the means to create electricity from glucose and oxygen, using an original architecture for the IBFC that provides efficient work inside a living organism. In the future these IBFCs will be required to power implanted devices to assist failing physiological functions in humans. The active ingredients of such IBFCs are glucose oxidase at the anode and laccase at the cathode. These enzymes are entrapped in a 3D network of conductive and insulated materials. This publication solves the issue of the sterilization of such a complex device, using gamma irradiation. A 12kGy dose was sufficient to show absence of implant infection in all the implantations performed. We also prove in vitro functioning of both bioelectrodes with a high dose of 42kGy.

Published
2016

26. Nanostructural determination of a lipid bilayer tethered to a gold substrate

Author

Marco Maccarini, Erik B. Watkins, Donald K. Martin, Bruce Cornell, Barry Stidder, Jean-Pierre Alcaraz, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Los Alamos National Laboratory (LANL), and SDx Tethered Membranes Pty Ltd

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Lipid Bilayers, Biophysics, Molecular Conformation, Nanotechnology, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biomimetic Materials, Molecule, General Materials Science, Lipid bilayer, Tethering, Chemistry, Bilayer, Cell Membrane, technology, industry, and agriculture, Substrate (chemistry), Biological membrane, Surfaces and Interfaces, General Chemistry, Living systems: Biomimetic Systems, 021001 nanoscience & nanotechnology, Transmembrane protein, 0104 chemical sciences, Nanostructures, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Membrane, lipids (amino acids, peptides, and proteins), Gold, 0210 nano-technology, Dimyristoylphosphatidylcholine, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], Biotechnology
Abstract

International audience; Tethered lipid bilayer membranes (tBLM) are planar membranes composed of free lipids and molecules tethered to a solid planar substrate providing a useful model of biological membranes for a wide range of biophysical studies and biotechnological applications. The properties of the tBLM depend on the free lipids and on the chemistry of the tethering molecules. We present a nanoscale characterization of a tBLM composed of deuterated 1,2-dimyristoyl-sn-glycero-3-phosphocholine (d-DMPC) free lipids, benzyl disulfide undecaethylene glycol phytanol (DLP) tethering molecules, and benzyl disulfiide tetraethylene glycol polar spacer molecules (PSM) used to control the areal density of tethering molecules through coadsorption. The use of selected isotopic substitution provides a way to distinguish the conformation and location of the tethered lipids from the free lipids and to elucidate how the two components influence the structure of the tBLM. These findings provide useful information to optimise the insertion of transmembrane proteins into the tethered bilayer system.

Published
2016

27. La biopile enzymatique à glucose/oxygène Quelques nuances de Grays

Author

Donald K. Martin, Sarra El Ichi-Ribault, Laurent Cortella, Jean-Pierre Alcaraz, Catherine Guimier-Pingault, Abdelkader Zebda, Philippe Cinquin, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ARC-Nucleart CEA Grenoble (NUCLEART), Laboratoire d'Innovation pour les Technologies des Energies Nouvelles et les nanomatériaux (LITEN), Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de L'Energie Solaire (INES), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS), and Centre Hospitalier Universitaire [Grenoble] (CHU)

Subjects
0301 basic medicine, Laccase, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, biology, Chemistry, Oxygen metabolism, Implant Infection, 02 engineering and technology, General Medicine, 021001 nanoscience & nanotechnology, General Biochemistry, Genetics and Molecular Biology, Anode, 03 medical and health sciences, 030104 developmental biology, biology.protein, Glucose oxidase, 0210 nano-technology, Gamma irradiation, Biomedical engineering
Abstract

International audience; > Une biopile enzymatique implantable est un dispositif produisant du courant uniquement à partir du glucose et de l'oxygène naturellement et constamment présents dans l'organisme. Les enzymes présentes aux électrodes oxydent le glucose et réduisent l'oxygène, ce qui génère un flux d'électrons dans un circuit électrique associé. Cette microcentrale électrique, qui peut fournir une tension de presque un volt, pourra alimen-ter sur une longue période la future génération de robots implantables. Tout dispositif médical implantable doit être stérilisé avant son implan-tation. Comme le principe actif de cette biopile est composé d'enzymes, la question de la stérilisation de ce nouveau type de dispositif s'est posée. < pacemaker [2]. Notre équipe a récemment implanté chez le rat une bioélectrode modifiée qui a conservé son activité après une durée de 167 jours [3]. Utilisation de l'ionisation pour la stérilisation du dispositif L'implantation d'un dispositif médical électronique alimenté par une biopile pose le problème de sa stérilisation. Pour les applications contenant du matériel biologique, ce qui est le cas de la biopile enzy-matique, l'autoclavage est proscrit car les enzymes sont dénaturées par la chaleur. Deux types de stérilisation à froid restent alors pos-sibles : l'une utilisant le peroxyde d'hydrogène (H 2 O 2) sous vide d'air, l'autre les radiations ionisantes. La stérilisation au H 2 O 2 est un procédé couramment utilisé dans les hôpi-taux pour les dispositifs médicaux implantables. Malheureusement, la structure des bioélectrodes est fortement dégradée sous l'effet du vide partiel. De plus, les enzymes sont presque totalement inactivées par la dose d'agent oxydant. Nous nous sommes donc intéressés à la stérilisa-tion via les rayonnements ionisants (RI). L'action des RI sur la cellule a été théorisée il y a un siècle grâce aux travaux de Marie Curie [4] et s'utilise couramment lors des traitements en radiothérapie. La réponse cellulaire aux RI permet d'appréhender les mécanismes de radio-sensibilité [5] (➜) et d'optimiser les traitements (radiothérapie FLASH [6]) (➜). Qu'est-ce qu'une biopile implantable ? La biopile enzymatique implantable que nous dévelop-pons permet de générer de l'énergie électrique grâce à des enzymes immobilisées sur des électrodes, à par-tir de glucose et d'oxygène, substrats présents dans l'organisme et potentiellement inépuisables. Tant que les enzymes fonctionnent, et que les substrats diffusent librement, il est possible de fournir du courant de façon quasi illimitée à des dispositifs médicaux électro-niques pouvant suppléer des fonctions défaillantes chez l'homme. Le principe de fonctionnement est illustré par la Figure 1. Le glucose est oxydé à la bioanode par la glucose oxydase qui fournit des électrons au circuit. Après passage dans le circuit électrique, ces électrons sont récupérés au niveau de la biocathode. À ce niveau, la laccase 1 sert à réduire le dioxygène en eau. Ces bioélectrodes ont la forme d'une pastille contenant les enzymes immobilisées dans un réseau tridimensionnel de matériau nanostructuré. La preuve de concept in vivo a été réalisée par Cinquin et al. en 2010 [1]. Cette biopile fournit actuellement suffisamment d'éner-gie (40 μW) pour alimenter des dispositifs tels qu'un 1 Oxydase avec du cuivre comme cofacteur. (➜) Voir la Synthèse de N. Foray et al., m/s n° 4, avril 2013, page 397 (➜) Voir la Nouvelle de V. Favaudon et al., m/s n° 2, février 2015, page 121 Alcaraz_DossierTechnique.indd 771 Alcaraz_DossierTechnique.indd 771

Published
2016

28. Biomimetic Membrane System Composed of a Composite Interpenetrating Hydrogel Film and a Lipid Bilayer

Author

Jean-Pierre Alcaraz, Barry Stidder, Donald K. Martin, Aziz Bakri, Nawel Khalef, Philippe Cinquin, Lavinia Liguori, Erik B. Watkins, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), TheREx, Institut Laue-Langevin (ILL), ILL, and chaire d'excellence RTRA fondation nanosciences, Pôle CSVSB UJF

Subjects
interpenetrating hydrogel, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Materials science, Composite number, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Biomaterials, chemistry.chemical_compound, Adsorption, Polymer chemistry, Electrochemistry, biomimetic membrane, Surface charge, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Lipid bilayer, polyelectrolyte, Layer by layer, 021001 nanoscience & nanotechnology, Condensed Matter Physics, Polyelectrolyte, lipid bilayer, 0104 chemical sciences, Electronic, Optical and Magnetic Materials, Membrane, Chemical engineering, chemistry, Agarose, 0210 nano-technology
Abstract

International audience; A simple way to form an interpenetrating hydrogel (IPH) by combining a layer-by-layer polyelectrolyte membrane with agarose is reported. The formed IPH membrane is more robust and easily manipulated compared to a polyelectrolyte membrane with the same number of layers. The IPH has good diffusion characteristics and retains the advantageous surface charge from the polyectrolyte composition that facilitates the adsorption of a stable lipid bilayer. The stable adsorption of a lipid bilayer on the IPH creates a biomimetic membrane system that is optimized for utilization in a diffusion chamber.

Published
2012

29. Identification of three tomato flower and fruit MADS-box proteins with a putative histone deacetylase binding domain

Author

Marcel Kuntz, Joël Gaffé, Claudie Lemercier, Jean-Pierre Alcaraz, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Biochimie et biophysique des systèmes intégrés (BBSI), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF), Plastes et Différenciation Cellulaire (PDC), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)

Subjects
0106 biological sciences, MESH: Introns, MESH: Sequence Homology, Amino Acid, Sequence Homology, MESH: Amino Acid Sequence, MESH: Base Sequence, MESH: RNA, Plant, 01 natural sciences, Solanum lycopersicum, Genes, Reporter, MESH: Lycopersicon esculentum, MESH: Genes, Plant, MADS-box, Plant Proteins, Genetics, 0303 health sciences, Histone deacetylase 5, MESH: Plant Proteins, Histone deacetylase 2, Exons, General Medicine, Cell biology, DNA-Binding Proteins, Amino Acid, RNA, Plant, Histone deacetylase binding, MESH: DNA Primers, DNA, Plant, Molecular Sequence Data, MESH: Sequence Alignment, MADS Domain Proteins, Flowers, Biology, Genes, Plant, Histone Deacetylases, MESH: MADS Domain Proteins, 03 medical and health sciences, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, Lycopersicon esculentum, MESH: DNA, Plant, Reporter, Transcription factor, DNA Primers, 030304 developmental biology, Binding Sites, MESH: Molecular Sequence Data, Sequence Homology, Amino Acid, Base Sequence, HDAC11, HDAC10, MESH: Genes, Reporter, DNA, Plant, MESH: Flowers, HDAC4, Introns, MESH: Histone Deacetylases, Genes, MESH: Binding Sites, RNA, MESH: Exons, Sequence Alignment, MESH: DNA-Binding Proteins, 010606 plant biology & botany
Abstract

International audience; MADS-box transcription factors play crucial roles in organ and cell differentiation in organisms ranging from yeast to humans. Most of the work on plant MADS-box proteins focused on their roles in floral development whereas less information is available on their function in fruit maturation. We cloned three distinct tomato cDNAs using a RT-PCR approach, encoding LeMADS1, LeMADS5 and LeMADS6 factors and whose mRNAs mostly accumulate in tomato flowers and fruits. Phylogeny analysis indicates that LeMADS1, 5 and 6 belong to the MEF2-like family. When transiently expressed in tobacco leaves or in human cells, LeMADS1, 5 and 6 are targeted to the cell nucleus. As the endogenous target genes of these putative transcription factors are unknown, the transcriptional activity of these proteins was characterized in a heterologous system and we showed that, when fused to a Gal4-DNA-binding domain, they repress the transcription of heterologous reporter genes. Since histone deacetylases control MEF2 transcriptional activity and since a putative histone deacetylase binding site was present in LeMADS1, 5 and 6, we tested the potential interaction between these factors and HDAC5 deacetylase. Surprisingly, in this heterologous system, LeMADS1, 5 and 6 interacted with HDAC5 N-terminal region. Our data suggest that, like mammalian MEF2A, plant MADS-box transcriptional activity might be regulated by enzymes controlling chromatin acetylation.

Published
2011

30. Plant lipid-associated fibrillin proteins condition jasmonate production under photosynthetic stress

Author

Abir Youssef, Joël Gaffé, Yec’han Laizet, Maryse A. Block, Dominique Pontier, Jean-Pierre Alcaraz, Eric Maréchal, Tony R. Larson, Marcel Kuntz, Plastes et Différenciation Cellulaire (PDC), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), CNAP, Department of Biology, University of York [York, UK], Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche Interdisciplinaire de Grenoble (IRIG), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), and Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)

Subjects
0106 biological sciences, plastoglobule, Photoinhibition, Arabidopsis thaliana, Plastoglobule, thylakoid, Arabidopsis, plant, Plant Science, 01 natural sciences, Anthocyanins, chemistry.chemical_compound, Jasmonate, Photosynthesis, plastid, 0303 health sciences, Jasmonic acid, Microfilament Proteins, food and beverages, Chloroplast, Biochemistry, Thylakoid, RNA Interference, jasmonic acid biosynthesis, triacylglycerol, photooxidative stress, fibrillin, Cyclopentanes, Biology, lipid associated protein, Fibrillins, 03 medical and health sciences, chloroplast, Microscopy, Electron, Transmission, Stress, Physiological, Genetics, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Oxylipins, Plastid, 030304 developmental biology, Arabidopsis Proteins, fungi, photosystem II, Photosystem II Protein Complex, Cell Biology, biology.organism_classification, chemistry, photosynthesis acclimation, 010606 plant biology & botany
Abstract

International audience; Summary The role of a subfamily of lipid globule-associated proteins, referred to as plant fibrillins (FIB1a, -1b, -2), was determined using a RNA interference (RNAi) strategy. We show that Arabidopsis plants with reduced levels of these plastid structural proteins are impaired in long-term acclimation to environmental constraint, namely photooxidative stress imposed by high light combined with cold. As a result, their photosynthetic apparatus is inefficiently protected. This leads to the prevalence of an abnormal granal and stromal membrane arrangement, as well as higher photosystem II photoinhibition under stress. The visible phenotype of FIB1-2 RNAi lines also includes retarded shoot growth and a deficit in anthocyanin accumulation under stress. All examined phenotypic effects of lower FIB levels are abolished by jasmonate (JA) treatment. An atypical expression pattern of several JA-induced genes was observed in RNAi plants. A JA-deficient mutant was found to share similar stress phenotypic characteristics with FIB RNAi plants. We conclude a new physiological role for JA, namely acclimation of chloroplasts, and that light/cold stress-related JA biosynthesis is conditioned by the accumulation of plastoglobule-associated FIB1-2 proteins. Consistent correlative data suggest that this FIB effect is mediated by plastoglobule (and triacylglycerol) accumulation as the potential site for initiating the chloroplast stress-related JA biosynthesis.

Published
2010

31. Fibrillin influence on plastid ultrastructure and pigment content in tomato fruit

Author

Joël Gaffé, Paul D. Fraser, Andrew J. Simkin, Peter M. Bramley, Jean-Pierre Carde, Marcel Kuntz, Jean-Pierre Alcaraz, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Plastes et différenciation cellulaire (PDC), European commission Agriculture and Fisheries program for the mobility of researchers (Contract No. FAIR-98-5002), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Laboratoire de physiologie cellulaire végétale (LPCV), and Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, Plastoglobule, macromolecular substances, Plant Science, MESH: Capsicum, Horticulture, Biology, Fibrillins, Thylakoids, Chloroplast, 01 natural sciences, Biochemistry, MESH: Microfilament Proteins, 03 medical and health sciences, MESH: Thylakoids, Solanum lycopersicum, Membrane pore, MESH: Lycopersicon esculentum, Chromoplast, Plastids, Lycopersicon esculentum, Thylakoid integrity, Plastid, Molecular Biology, Carotenoid, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Microfilament Proteins, food and beverages, Ripening, MESH: Plastids, General Medicine, Plants, Genetically Modified, Fruit ripening, Carotenoids, MESH: Plants, Genetically Modified, chemistry, Fruit, Thylakoid, MESH: Carotenoids, Capsicum, MESH: Fruit, Fibrillin, 010606 plant biology & botany
Abstract

International audience; The protein termed fibrillin is involved in the formation of lipoprotein structures, such as plastoglobules and fibrils in certain chromoplast types, which have been implicated in the over-production of pigments due to a sink effect. In order to examine its effect in differentiating chromoplasts of a non-fibrillar type, the pepper fibrillin gene was expressed in tomato fruit. Both the transcript and protein were found to accumulate during tomato fruit ripening from an early mature green stage. However, formation of carotenoid deposition structures in tomato chromoplasts, such as fibrils, was not observed. Nevertheless, a two-fold increase in carotenoid content and associated carotenoid derived flavour volatiles (6-methyl-5-hepten-2-one, geranylacetone, beta-ionone and beta-cyclocitral) was observed. An unexpected phenotypic observation in the transgenic fruit was the delayed loss of thylakoids in differentiating chromoplasts, leading to the transient formation of plastids exhibiting a typical chromoplastic zone adjacent to a protected chloroplastic zone with preserved thylakoids. An in vitro assay has been developed to monitor fibrillin activity on thylakoids: data were obtained suggesting a membrane protection role for fibrillin, more specifically against moderate uncoupling effects.

Published
2007

32. Réacteur implantable biocompatible

Author

Philippe Cinquin, Donald Martin, jean-pierre alcaraz, Geraldine Penven, ZOPPIS, Catherine, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), and VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract

The invention relates to a bioreactor obtained by compression of a mixture comprising an enzyme and a conductor, the inactive surfaces of the bioreactor being coated with impermeable parylene (32), and each active surface of the bioreactor being coated with a nano-porous membrane of parylene (40) glued along the periphery thereof., L'invention concerne un bioréacteur obtenu par compression d'un mélange comprenant une enzyme et un conducteur, les faces inactives de ce bioréacteur étant revêtues de parylène imperméable (32), chaque face active de ce bioréacteur étant recouverte d'une membrane nanoporeuse de parylène (40) collée à la périphérie de celle-ci.

Published
2015

33. Biocompatible implantable biofuel cell

Author

Sarra El Ichi, Philippe Cinquin, Jean Boutonnat, Jean-Pierre Alcaraz, François Boucher, Abdelkader Zebda, Donald K. Martin, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), EPHE, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), and Alcaraz, Jean-Pierre

Subjects
In vivo biocompatibility, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Materials science, Chitosan membrane, Biofuel, Electrode, Nanotechnology, Power output, Biocompatible material, 7. Clean energy, ComputingMilieux_MISCELLANEOUS, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Biomedical engineering
Abstract

The present work demonstrates the in vivo biocompatibility and operation of a biofuel cell enclosed by a chitosan membrane. The measured power output in the range of 6.2 to 20.7 µW cm−2 (applied current from 10 to 70 µA) indicated that glucose and oxygen can reach the enzymes in the 3D matrix without any need for a buffer solution in the implant or a hydration step. This is very important to simplify the preparation and sterilization steps, to avoid contamination and to favour the close communication between the device and body fluids. This optimized biofuel cell is now being applied to supplying power for a leadless pacemaker.

Published
2014

34. A Novel Role of Water-Soluble Chlorophyll Proteins in the Transitory Storage of Chorophyllide

Author

Christiane Reinbothe, Hiroyuki Satoh, Steffen Reinbothe, and Jean-Pierre Alcaraz

Subjects
biology, Physiology, food and beverages, macromolecular substances, Plant Science, biology.organism_classification, Photosynthesis, Chloroplast, chemistry.chemical_compound, Membrane protein, Biochemistry, chemistry, Thylakoid, Chlorophyll, Botany, Genetics, Hordeum vulgare, Plastid, Chenopodiaceae
Abstract

All chlorophyll (Chl)-binding proteins involved in photosynthesis of higher plants are hydrophobic membrane proteins integrated into the thylakoids. However, a different category of Chl-binding proteins, the so-called water-soluble Chl proteins (WSCPs), was found in members of the Brassicaceae, Polygonaceae, Chenopodiaceae, and Amaranthaceae families. WSCPs from different plant species bind Chl a and Chl b in different ratios. Some members of the WSCP family are induced after drought and heat stress as well as leaf detachment. It has been proposed that this group of proteins might have a physiological function in the Chl degradation pathway. We demonstrate here that a protein that shared sequence homology to WSCPs accumulated in etiolated barley (Hordeum vulgare) seedlings exposed to light for 2 h. The novel 22-kD protein was attached to the outer envelope of barley etiochloroplasts, and import of the 27-kD precursor was light dependent and induced after feeding the isolated plastids the tetrapyrrole precursor 5-aminolevulinic acid. HPLC analyses and spectroscopic pigment measurements of acetone-extracted pigments showed that the 22-kD protein is complexed with chlorophyllide. We propose a novel role of WSCPs as pigment carriers operating during light-induced chloroplast development.

Published
2004

35. [Untitled]

Author

Reinhold G. Herrmann, Rainer M. Maier, Jean-Pierre Alcaraz, Régis Mache, Annick Cottet, and Christian Schmitz-Linneweber

Subjects
Genetics, Plastid chromosome, Base pair, Reading frame, Nucleic acid sequence, food and beverages, Chromosome, Plant Science, General Medicine, Biology, DNA sequencing, Chloroplast chromosome, Agronomy and Crop Science, Gene
Abstract

The chloroplast chromosome of spinach (Spinacia oleracea) is a double-stranded circular DNA molecule of 150 725 nucleotide pairs. A comparison of this chromosome with those of the three other autotrophic dicotyledons for which complete DNA sequences of plastid chromosomes are available confirms a conserved overall structure. Three classes of open reading frames were distinguished: (1) genes of known function which include 108 unique loci, (2) three hypothetical chloroplast reading frames (ycfs) that are highly conserved interspecifically, and (3) species-specific or rapidly diverging 'open reading frames'. A detailed transcript study of one of the latter (ycf15) shows that these loci may be transcribed, but do not constitute protein-coding genes.

Published
2001

36. Single glucose biofuel cells implanted in rats power electronic devices

Author

Michael Holzinger, Serge Cosnier, H. Lamraoui, Philippe Cinquin, Fabien Giroud, Abdelkader Zebda, A. Le Goff, François Boucher, Karine Gorgy, Chantal Gondran, Jean-Pierre Alcaraz, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Département de Chimie Moléculaire - Biosystèmes Electrochimiques et Analytiques (DCM - BEA), Département de Chimie Moléculaire (DCM), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-IMAG-PRETA), Techniques de l'Informatique et de la Microélectronique pour l'Architecture des systèmes intégrés (TIMA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Interdisciplinary Energy program of CNRS PR10-1-1, Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Techniques of Informatics and Microelectronics for integrated systems Architecture (TIMA), and Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)

Subjects
Materials science, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Bioelectric Energy Sources, 02 engineering and technology, Biosensing Techniques, 010402 general chemistry, 7. Clean energy, 01 natural sciences, Article, Glucose Oxidase, [CHIM.GENI]Chemical Sciences/Chemical engineering, Animals, Glucose oxidase, Power output, carbon nanotube, [INFO.INFO-BT]Computer Science [cs]/Biotechnology, Enzymatic biofuel cell, implantable medical device, Diode, Power density, Multidisciplinary, biology, Nanotubes, Carbon, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Power (physics), Body Fluids, Rats, glucose biofuel cell, Glucose, Biochemistry, biology.protein, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, Oxidation-Reduction, Biofuel Cells, Biomedical engineering
Abstract

5 pages; International audience; We describe the first implanted glucose biofuel cell (GBFC) that is capable of generating sufficient power from a mammal's body fluids to act as the sole power source for electronic devices. This GBFC is based on carbon nanotube/enzyme electrodes, which utilize glucose oxidase for glucose oxidation and laccase for dioxygen reduction. The GBFC, implanted in the abdominal cavity of a rat, produces an average open-circuit voltage of 0.57 V. This implanted GBFC delivered a power output of 38.7 μW, which corresponded to a power density of 193.5 μW cm(-2) and a volumetric power of 161 μW mL(-1). We demonstrate that one single implanted enzymatic GBFC can power a light-emitting diode (LED), or a digital thermometer. In addition, no signs of rejection or inflammation were observed after 110 days implantation in the rat.

Published
2013

37. A glucose biofuel cell implanted in rats

Author

Fabien Giroud, Aymeric Pellissier, Philippe Cinquin, Simon Mazabrard, Serge Cosnier, Jean-Pierre Alcaraz, Chantal Gondran, Paolo Porcu, Karine Gorgy, François Lenouvel, Stephane Mathe, François Boucher, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Département de Chimie Moléculaire - Biosystèmes Electrochimiques et Analytiques (DCM - BEA), Département de Chimie Moléculaire (DCM), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Joseph Fourier - Grenoble 1 (UJF), Physiologie cardio-Respiratoire Expérimentale Théorique et Appliquée (TIMC-IMAG-PRETA), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Plastes et Différenciation Cellulaire (PDC), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), ANR (Agence Nationale de la Recherche), EMERGENCE (Rhone-Alpes Region program) and Floralis (UJF's subsidiary), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, MESH: Oxidation-Reduction, MESH: Hydrogen-Ion Concentration, Time Factors, Biochemistry/Membrane Proteins and Energy Transduction, Bioelectric Energy Sources, Ubiquinone, lcsh:Medicine, 02 engineering and technology, 7. Clean energy, 01 natural sciences, Chloride, Biotechnology/Biocatalysis, Implants, Experimental, Urea, Glucose oxidase, MESH: Animals, MESH: Ubiquinone, Enzymatic biofuel cell, lcsh:Science, chemistry.chemical_classification, Chemistry/Physical, Inorganic, and Analytical Chemistry, Multidisciplinary, biology, Hydrogen-Ion Concentration, 021001 nanoscience & nanotechnology, Urease, MESH: Glucose, Biochemistry, Biophysics/Membrane Proteins and Energy Transduction, Physiology/Integrative Physiology, Biotechnology/Bioengineering, 0210 nano-technology, MESH: Bioelectric Energy Sources, Oxidation-Reduction, Catechol Oxidase, Research Article, medicine.drug, MESH: Rats, MESH: Urease, Biochemistry/Biocatalysis, MESH: Implants, Experimental, Chemistry/Applied Chemistry, MESH: Catechol Oxidase, 010402 general chemistry, MESH: Prosthesis Implantation, Redox, Prosthesis Implantation, Glucose Oxidase, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, Chemistry/Biochemistry, Biophysics/Biocatalysis, Rats, Wistar, Catechol oxidase, Electrodes, MESH: Urea, lcsh:R, MESH: Time Factors, MESH: Electrodes, MESH: Rats, Wistar, MESH: Male, Rats, 0104 chemical sciences, Anode, Glucose, Enzyme, chemistry, biology.protein, Biophysics, MESH: Glucose Oxidase, Surgery, lcsh:Q
Abstract

International audience; Powering future generations of implanted medical devices will require cumbersome transcutaneous energy transfer or harvesting energy from the human body. No functional solution that harvests power from the body is currently available, despite attempts to use the Seebeck thermoelectric effect, vibrations or body movements. Glucose fuel cells appear more promising, since they produce electrical energy from glucose and dioxygen, two substrates present in physiological fluids. The most powerful ones, Glucose BioFuel Cells (GBFCs), are based on enzymes electrically wired by redox mediators. However, GBFCs cannot be implanted in animals, mainly because the enzymes they rely on either require low pH or are inhibited by chloride or urate anions, present in the Extra Cellular Fluid (ECF). Here we present the first functional implantable GBFC, working in the retroperitoneal space of freely moving rats. The breakthrough relies on the design of a new family of GBFCs, characterized by an innovative and simple mechanical confinement of various enzymes and redox mediators: enzymes are no longer covalently bound to the surface of the electron collectors, which enables use of a wide variety of enzymes and redox mediators, augments the quantity of active enzymes, and simplifies GBFC construction. Our most efficient GBFC was based on composite graphite discs containing glucose oxidase and ubiquinone at the anode, polyphenol oxidase (PPO) and quinone at the cathode. PPO reduces dioxygen into water, at pH 7 and in the presence of chloride ions and urates at physiological concentrations. This GBFC, with electrodes of 0.133 mL, produced a peak specific power of 24.4 microW mL(-1), which is better than pacemakers' requirements and paves the way for the development of a new generation of implantable artificial organs, covering a wide range of medical applications.

Published
2010

38. Intraplastidial trafficking of a phage-type RNA polymerase is mediated by a thylacoïd RING-H2 protein

Author

Silva Lerbs-Mache, Thierry Lagrange, Mohamed-Ali Hakimi, Pankaj Jaiswal, Florence Courtois, Emilie Demarsy, Laurence Maréchal-Drouard, Jacinthe Azevedo, Jean-Pierre Alcaraz, Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Plastes et différenciation cellulaire (PDC), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Laboratoire Génome et développement des plantes (LGDP), Université de Perpignan Via Domitia (UPVD)-Centre National de la Recherche Scientifique (CNRS), Department of Plant Breeding and Genetics, Cornell University [New York], and Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0106 biological sciences, Light, Arabidopsis, MESH: Amino Acid Sequence, Thylakoids, 01 natural sciences, chemistry.chemical_compound, MESH: Saccharomyces cerevisiae Proteins, MESH: Thylakoids, Gene Expression Regulation, Plant, Transcription (biology), RNA, Ribosomal, 16S, RNA polymerase, MESH: Arabidopsis, Bacteriophages, Promoter Regions, Genetic, MESH: Organ Specificity, 0303 health sciences, Multidisciplinary, food and beverages, MESH: Transcription Factors, DNA-Directed RNA Polymerases, Biological Sciences, Transport protein, Cell biology, MESH: RNA, Ribosomal, 16S, DNA-Binding Proteins, Chloroplast, MESH: Promoter Regions (Genetics), MESH: Intracellular Membranes, Protein Transport, Transmembrane domain, Organ Specificity, Thylakoid, Protein Binding, MESH: Protein Transport, Saccharomyces cerevisiae Proteins, Molecular Sequence Data, MESH: Arabidopsis Proteins, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Two-Hybrid System Techniques, DNA-binding protein, 03 medical and health sciences, Two-Hybrid System Techniques, MESH: Gene Library, MESH: Protein Binding, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Bacteriophages, Amino Acid Sequence, RNA, Messenger, MESH: Gene Expression Regulation, Plant, Plastid, MESH: RNA, Messenger, Gene Library, 030304 developmental biology, MESH: Molecular Sequence Data, Arabidopsis Proteins, Intracellular Membranes, Molecular biology, MESH: Light, MESH: DNA-Directed RNA Polymerases, chemistry, Transcription Factors, 010606 plant biology & botany
Abstract

The plastid genome of dicotyledonous plants is transcribed by three different RNA polymerases; an eubacterial-type enzyme, PEP; and two phage-type enzymes, RPOTp and RPOTmp. RPOTp plays an important role in chloroplast transcription, biogenesis, and mesophyll cell proliferation. RPOTmp fulfills a specific function in the transcription of the rrn operon in proplasts/amyloplasts during seed imbibition/germination and a more general function in chloroplasts during later developmental stages. In chloroplasts, RPOTmp is tightly associated with thylakoid membranes indicating that functional switching of RPOTmp is connected to thylakoid association. By using the yeast two-hybrid system, we have identified two proteins that interact with RPOTmp. The two proteins are very similar, both characterized by three N-terminal transmembrane domains and a C-terminal RING domain. We show that at least one of these proteins is an intrinsic thylakoid membrane protein that fixes RPOTmp on the stromal side of the thylakoid membrane, probably via the RING domain. A model is presented in which light by triggering the synthesis of the RING protein determines membrane association and functional switching of RPOTmp.

Published
2008

39. Improvement of pCVD442, a suicide plasmid for gene allele exchange in bacteria

Author

Nadège Philippe, Dominique Schneider, Evelyne Coursange, Jean-Pierre Alcaraz, Johannes Geiselmann, Laboratoire Adaptation et pathogénie des micro-organismes [Grenoble] (LAPM), Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Plastes et différenciation cellulaire (PDC), and Université Joseph Fourier - Grenoble 1 (UJF)

Subjects
MESH: DNA Primers, Biology, Bacterial genetics, 03 medical and health sciences, Plasmid, Amp resistance, MESH: Plasmids, Escherichia coli, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Insertion sequence, Molecular Biology, Gene, Alleles, 030304 developmental biology, DNA Primers, Genetics, 0303 health sciences, 030306 microbiology, MESH: Escherichia coli, Point mutation, MESH: Alleles, Genes, Transgenic, Suicide, Suicide gene, Transformation (genetics), MESH: Genes, Transgenic, Suicide, MESH: DNA Transposable Elements, DNA Transposable Elements, Transformation, Bacterial, MESH: Transformation, Bacterial, Plasmids
Abstract

Allelic exchange experiments allow investigation of the functions of many unknown genes identified during the sequencing of entire genomes. Isogenic strains differing by only specific mutations can be constructed. Among other tools, suicide plasmids are widely used for this task. They present many advantages because they leave no scars on the chromosome, and therefore allow combining several mutations in the same genetic background. While using the previously described pCVD442 suicide plasmid [Infect. Immun. 59 (1991) 4310], we found untargeted recombination events due to the presence of an IS1 element on this plasmid. The plasmid was therefore improved by removal of the IS1 element. We also replaced the bla gene of pCVD442, conferring ampicillin resistance, by the cat gene conferring chloramphenicol resistance, leading to the new suicide plasmid pDS132. The plasmid was entirely sequenced. We demonstrate that this new vector can be easily used to introduce various types of mutations into different genetics backgrounds: removal of IS elements, introduction of point mutations or deletions. It can be introduced into bacterial strains by either transformation or conjugation.

Published
2004

41. In vitro characterization of a plastid terminal oxidase (PTOX)

Author

Anne-Marie Labouré, Eve-Marie Josse, Jean-Pierre Alcaraz, and Marcel Kuntz

Subjects
Alternative oxidase, Iron, Molecular Sequence Data, Malates, Plastoquinone, Biology, Sodium Chloride, Biochemistry, Plastid terminal oxidase, Citric Acid, Substrate Specificity, chemistry.chemical_compound, Quinone binding, Oxygen Consumption, Gallic Acid, Consensus Sequence, Escherichia coli, Amino Acid Sequence, Enzyme Inhibitors, Oxidase test, Binding Sites, Arabidopsis Proteins, Escherichia coli Proteins, Cell Membrane, Quinones, Temperature, Chlororespiration, Hydrogen-Ion Concentration, Benzoquinone, chemistry, Octyl gallate, Oxidoreductases
Abstract

The plastid terminal oxidase (PTOX) encoded by the Arabidopsis IMMUTANS gene was expressed in Escherichia coli cells and its quinone/oxygen oxidoreductase activity monitored in isolated bacterial membranes using NADH as an electron donor. Specificity for plastoquinone was observed. Neither ubiquinone, duroquinone, phylloquinone nor benzoquinone could substitute for plastoquinone in this assay. However, duroquinol (fully reduced chemically) was an accepted substrate. Iron is also required and cannot be substituted by Cu(2+), Zn(2+) or Mn(2+). This plastoquinol oxidase activity is independent of temperature over the 15-40 degrees C range but increases with pH (from 5.5 to 9.0). Unlike higher plant mitochondrial alternative oxidases, to which PTOX shows sequence similarity (but also differences, especially in a putative quinone binding site and in cysteine conservation), PTOX activity does not appear to be regulated by pyruvate or any other tested sugar, nor by AMP. Its activity decreases, however, with increasing salt (NaCl or KCl) concentration. Various quinone analogues were tested for their inhibitory activity on PTOX. Pyrogallol analogues were found to be inhibitors, especially octyl gallate (I50 = 0.4 microM ) that appears far more potent than propyl gallate or gallic acid. Thus, octyl gallate is a useful inhibitor for future in vivo or in organello studies aimed at studying the roles of PTOX in chlororespiration and as a cofactor for carotenoid biosynthesis.

Published
2003

42. Tackling the Concept of Symbiotic Implantable Medical Devices with Nanobiotechnologies

Author

Jean-Pierre Alcaraz, Donald K. Martin, Philippe Cinquin, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), and Alcaraz, Jean-Pierre

Subjects
0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Computer science, Biocompatible Materials, 02 engineering and technology, Regenerative Medicine, Applied Microbiology and Biotechnology, 03 medical and health sciences, Human–computer interaction, Humans, Nanotechnology, Implanted device, ComputingMilieux_MISCELLANEOUS, Prostheses and Implants, General Medicine, 021001 nanoscience & nanotechnology, Biocompatible material, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, 3. Good health, Encapsulation (networking), 030104 developmental biology, Equipment and Supplies, Molecular Medicine, Bioinspiration, 0210 nano-technology, Biotechnology
Abstract

This review takes an approach to implanted medical devices that considers whether the intention of the implanted device is to have any communication of energy or materials with the body. The first part describes some specific examples of three different classes of implants, analyzed with regards to the type of signal sent to cells. Through several examples, the authors describe that a one way signaling to the body leads to encapsulation or degradation. In most cases, those phenomena do not lead to major problems. However, encapsulation or degradation are critical for new kinds of medical devices capable of duplex communication, which are defined in this review as symbiotic devices. The concept the authors propose is that implanted medical devices that need to be symbiotic with the body also need to be designed with an intended duplex communication of energy and materials with the body. This extends the definition of a biocompatible system to one that requires stable exchange of materials between the implanted device and the body. Having this novel concept in mind will guide research in a new field between medical implant and regenerative medicine to create actual symbiotic devices.

43. Physiological considerations for the design and integration of bioinspired implantable biofuel cells

Author

jean-pierre alcaraz, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université Grenoble Alpes, Donald Martin, and Philippe Cinquin

Subjects
Energy, Membrane biomimétique, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Biofuel cell, Polyelectrolyte, Biomimetic membrane, Polyelectrolytes, Membrane proteins, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Matériau implantable, Biopile, Implantable material, Protéines membranaires, Energie
Abstract

We believe that in the near future micro-robots or artificial implanted organs can replace failing essential organs. Lithium batteries of cardiac pacemakers are well adapted to operate for years into sick patients. However, for next generation energy intensive implanted devices, longevity and volumic power of these batteries have to be improved.We chose two biomimetic approaches to create bioinspired biofuel cells: the enzymatic biofuel cells generate electrical current from the oxidation and the reduction of organic or inorganic compounds. The biomimetic biofuel cell generate an electrical potential from ion transfer across a biomimetic membrane.The enzymatic biofuel.cells, utilizing glucose and oxygen, are theorically able to work almost indefinitely as their substrates are always present in the body fluids. However, the biocompatibility and the long-term performance of these biofuel cells for a human implantation remain a real bottleneck. This thesis describes the design and the implantation of of new enzymatic biofuel cells in different animal models. The implantation of such devices is challenging and we brought creative solutions with a physiological point of view by addressing biocompatibility problems and electrical measurement techniques. We are now capable to implant these biofuel cells in big animals by analyzing the performances of the biofuel cell in real time.This thesis initiates the biomimetic biofuel cell concept. It consists in membrane transport protein (i.e ion channels) incorporated in a biomimetic membrane. The building of a biomimetic device demonstrates the transformation of a NaCl gradient into a proton gradient. We also generate a 20 mV voltage with a 38 mm² flat membrane. This biomimetic membrane containing the NhaA sodium/ proton exchanger is stable for more than two weeks.; On peut imaginer dans un futur proche que des micro-robots implantés pourront suppléer la défaillance de certaines fonctions essentielles. C’est déjà le cas avec les stimulateurs cardiaques dont les piles au lithium sont bien adaptées à leur fonctionnement pendant des années de vie du patient. Cependant, pour des systèmes plus gourmands en énergie, il convient d’améliorer la longévité et la puissance volumique de ces piles. La stratégie que nous avons choisie est basée sur une approche biomimétique et deux voies ont été suivies pour créer une biopile bioinspirée : les biopiles enzymatiques génèrent un courant électrique à partir de l’oxydation de molécules organiques et la réduction d’oxygène en eau. Les biopiles à base de membranes biomimétiques génèrent un potentiel électrique à partir du transfert d’ions au travers une membrane biomimétique.Les biopiles enzymatiques, qui utilisent par exemple le glucose et l’oxygène, sont théoriquement capables de fonctionner indéfiniment car ces substrats sont toujours présents dans l’organisme. Cependant, la biocompatibilité et la performance à long terme de ces biopiles restent des verrous pour leur mise en œuvre chez l’homme. Cette thèse décrit la conception et l’implantation de nouvelles biopiles enzymatiques chez différents modèles animaux. Leur implantation constitue un véritable défi technologique et nous amenons des solutions guidées par la physiologie en abordant les problèmes de biocompatibilité mais aussi de techniques de mesure électrique.Nous sommes maintenant capables d’implanter ces biopiles chez de gros animaux en analysant en temps réel les performances de la biopile implantée.Cette thèse développe également le concept de biopile à base de membranes biomimétiques. Il s’agit d’une biopile mettant en œuvre des protéines de transport (par exemple des canaux ioniques) insérées dans des membranes biomimétiques. Nous avons démontré la faisabilité de la transformation d’un gradient de NaCl en gradient de protons. Nous avons aussi réussi à générer une différence de potentiel de 20 millivolts avec une membrane plane de 38 mm². Cette membrane biomimétique, contenant l’échangeur sodium/proton NhaA, est stable pendant plus de 15 jours.

44. Implantable intestinal reactor

Author

Philippe Cinquin, Dominique Schneider, Max Maurin, Donald Martin, Sarra El Ichi, Abdelkader Zebda, jean-pierre alcaraz, Fabian Reche, Patrick Tuvignon, Jacques Thélu, Audrey Legouëllec, Bertrand Toussaint, Systèmes Nanobiotechnologiques et Biomimétiques (TIMC-IMAG-SyNaBi), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Génomique et Évolution des Microorganismes (TIMC-IMAG-GEM), Centre Hospitalier Universitaire [Grenoble] (CHU), Thérapeutique Recombinante Expérimentale (TIMC-IMAG-TheREx), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), and Alcaraz, Jean-Pierre

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.BIO] Life Sciences [q-bio]/Biotechnology

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