47 results on '"Savin, Thierry"'
Search Results
2. New two-parameter constitutive models for rubber-like materials: Revisiting the relationship between single chain stretch and continuum deformation
- Author
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Tan, Ian, Biggins, John S., and Savin, Thierry
- Published
- 2024
- Full Text
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3. Fingering instabilities in tissue invasion: an active fluid model
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Bogdan, Michał and Savin, Thierry
- Subjects
Physics - Biological Physics ,Condensed Matter - Soft Condensed Matter ,Quantitative Biology - Tissues and Organs - Abstract
Metastatic tumors often invade healthy neighboring tissues by forming multicellular finger-like protrusions emerging from the cancer mass. To understand the mechanical context behind this phenomenon, we here develop a minimalist fluid model of a self-propelled, growing biological tissue. The theory involves only four mechanical parameters and remains analytically trackable in various settings. As an application of the model, we study the evolution of a 2D circular droplet made of our active and expanding fluid, and embedded in a passive non-growing tissue. This system could be used to model the evolution of a carcinoma in an epithelial layer. We find that our description can explain the propensity of tumor tissues to fingering instabilities, as conditioned by both the magnitude of active traction and the growth kinetics. We are also able to derive predictions for the tumor size at the onset of metastasis, and for the number of subsequent invasive fingers. Our active fluid model may help describe a wider range of biological processes, including wound healing and developmental patterning.
- Published
- 2018
4. Errors in energy landscapes measured with particle tracking
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Bogdan, Michał and Savin, Thierry
- Subjects
Condensed Matter - Soft Condensed Matter - Abstract
Tracking Brownian particles is often employed to map the energy landscape they explore. Such measurements have been exploited to study many biological processes and interactions in soft materials. Yet, video tracking is irremediably contaminated by localization errors originating from two imaging artifacts: the "static" errors come from signal noise, and the "dynamic" errors arise from the motion blur due to finite frame acquisition time. We show that these errors result in systematic and non-trivial biases in the measured energy landscapes. We derive a relationship between the true and the measured potential that elucidates, among other aberrations, the presence of false double-well minima in the apparent potentials reported in recent studies. We further assess several canonical trapping and pair-interaction potentials, by using our analytically derived results and Brownian dynamics simulations. In particular, we show that the apparent spring stiffness of harmonic potentials (such as optical traps) is increased by dynamic errors, but decreased by static errors. Our formula allows for the development of efficient corrections schemes, which we also present in this paper., Comment: 10 pages, 6 figures
- Published
- 2017
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5. New Two-Parameter Constitutive Models for Rubber-Like Materials: Revisiting the Relationship between Single Chain Stretch and Continuum Deformation
- Author
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Tan, Ian, primary, Biggins, John S., additional, and Savin, Thierry, additional
- Published
- 2024
- Full Text
- View/download PDF
6. Solution fibre spinning technique for the fabrication of tuneable decellularised matrix-laden fibres and fibrous micromembranes
- Author
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Li, Zhaoying, Tuffin, Jack, Lei, Iek M., Ruggeri, Francesco S., Lewis, Natasha S., Gill, Elisabeth L., Savin, Thierry, Huleihel, Luai, Badylak, Stephen F., Knowles, Tuomas, Satchell, Simon C., Welsh, Gavin I., Saleem, Moin A., and Huang, Yan Yan Shery
- Published
- 2018
- Full Text
- View/download PDF
7. Errors in Energy Landscapes Measured with Particle Tracking
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Bogdan, Michał J. and Savin, Thierry
- Published
- 2018
- Full Text
- View/download PDF
8. Chapter 4. Biomimetics of Structural Colours: Materials, Methods and Applications
- Author
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Dumanli, Ahu Gümrah, primary and Savin, Thierry, additional
- Published
- 2019
- Full Text
- View/download PDF
9. A magnetically actuated, optically sensed tensile testing method for mechanical characterization of soft biological tissues
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Rosalia, Luca, primary, Hallou, Adrien, additional, Cochrane, Laurence, additional, and Savin, Thierry, additional
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- 2023
- Full Text
- View/download PDF
10. A magnetically actuated, optically sensed tensile testing method for mechanical characterisation of soft biological tissues
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Rosalia, Luca, primary, Hallou, Adrien, additional, Cochrane, Laurence, additional, and Savin, Thierry, additional
- Published
- 2022
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11. Fibers with Integrated Mechanochemical Switches: Minimalistic Design Principles Derived from Fibronectin
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Peleg, Orit, Savin, Thierry, Kolmakov, German V., Salib, Isaac G., Balazs, Anna C., Kröger, Martin, and Vogel, Viola
- Published
- 2012
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12. Thermodynamic formulation of flowing soft matter with transient forces
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Savin, Thierry, Briels, Wim J., and Öttinger, Hans Christian
- Published
- 2013
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13. On the growth and form of the gut
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Savin, Thierry, Kurpios, Natasza A., Shyer, Amy E., Florescu, Patricia, Liang, Haiyi, Mahadevan, L., and Tabin, Clifford J.
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Digestive organs -- Growth -- Structure ,Morphogenesis -- Research ,Company growth ,Environmental issues ,Science and technology ,Zoology and wildlife conservation - Abstract
The developing vertebrate gut tube forms a reproducible looped pattern as it grows into the body cavity. Here we use developmental experiments to eliminate alternative models and show that gut looping morphogenesis is driven by the homogeneous and isotropic forces that arise from the relative growth between the gut tube and the anchoring dorsal mesenteric sheet, tissues that grow at different rates. A simple physical mimic, using a differentially strained composite of a pliable rubber tube and a soft latex sheet is consistent with this mechanism and produces similar patterns. We devise a mathematical theory and a computational model for the number, size and shape of intestinal loops based solely on the measurable geometry, elasticity and relative growth of the tissues. The predictions of our theory are quantitatively consistent with observations of intestinal loops at different stages of development in the chick embryo. Our model also accounts for the qualitative and quantitative variation in the distinct gut looping patterns seen in a variety of species including quail, finch and mouse, illuminating how the simple macroscopic mechanics of differential growth drives the morphology of the developing gut., Understanding morphogenesis, the origin of shape in anatomical structures, organs and organisms, has always been a central goal of developmental biology. Historically, the subject focused on the morphology and dynamics [...]
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- 2011
- Full Text
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14. Fingering instabilities in tissue invasion: an active fluid model
- Author
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Bogdan, Michał J, Savin, Thierry, Savin, Thierry [0000-0002-3956-7077], and Apollo - University of Cambridge Repository
- Subjects
fingering instabilities ,metastasis ,lcsh:Q ,lcsh:Science ,tissue invasion ,active fluids - Abstract
Metastatic tumours often invade healthy neighbouring tissues by forming multicellular finger-like protrusions emerging from the cancer mass. To understand the mechanical context behind this phenomenon, we here develop a minimalist fluid model of a self-propelled, growing biological tissue. The theory involves only four mechanical parameters and remains analytically trackable in various settings. As an application of the model, we study the evolution of a two-dimensional circular droplet made of our active and expanding fluid, and embedded in a passive non-growing tissue. This system could be used to model the evolution of a carcinoma in an epithelial layer. We find that our description can explain the propensity of tumour tissues to fingering instabilities, as conditioned by the magnitude of active traction and the growth kinetics. We are also able to derive predictions for the tumour size at the onset of metastasis, and for the number of subsequent invasive fingers. Our active fluid model may help describe a wider range of biological processes, including wound healing and developmental patterning.
- Published
- 2018
15. Static and Dynamic Errors in Particle Tracking Microrheology
- Author
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Savin, Thierry and Doyle, Patrick S.
- Published
- 2005
- Full Text
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16. Nonequilibrium thermodynamics of an interface
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Schweizer, Marco, Öttinger, Hans Christian, Savin, Thierry, Savin, Thierry [0000-0002-3956-7077], and Apollo - University of Cambridge Repository
- Subjects
0915 Interdisciplinary Engineering - Abstract
Interfacial thermodynamics has deep ramifications in understanding the boundary conditions of transport theories. We present a formulation of local equilibrium for interfaces that extends the thermodynamics of the "dividing surface," as introduced by Gibbs, to nonequilibrium settings such as evaporation or condensation. By identifying the precise position of the dividing surface in the interfacial region with a gauge degree of freedom, we exploit gauge-invariance requirements to consistently define the intensive variables for the interface. The model is verified under stringent conditions by employing high-precision nonequilibrium molecular-dynamics simulations of a coexisting vapor-liquid Lennard-Jones fluid. We conclude that the interfacial temperature is determined using the surface tension as a "thermometer," and it can be significantly different from the temperatures of the adjacent phases. Our findings lay foundations for nonequilibrium interfacial thermodynamics.
- Published
- 2016
17. Thermodynamic formulation of flowing soft matter with transient forces
- Author
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Savin, Thierry, Briels, Wim, Öttinger, Hans, Savin, Thierry, Briels, Wim, and Öttinger, Hans
- Abstract
The Responsive Particle Dynamics model is a very efficient method to account for the transient forces present in complex fluids, such as solutions of entangled polymers. This coarse-grained model considers a solution of particles that are made of a core and a corona. The cores typically interact through conservative interactions, while the coronae transiently penetrate each other to form short-lived temporary interactions, typically of entropic origin. In this study, we reformulate the resulting rheological model within the general framework of nonequilibrium thermodynamics called General Equation for the Nonequilibrium Reversible-Irreversible Coupling. This allows us to determine the consistency of the model, from a mechanistic and thermodynamic point of view, and to isolate the reversible and irreversible contributions to the dynamics of the model system
- Published
- 2018
18. Fingering instabilities in tissue invasion: an active fluid model
- Author
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Bogdan, Michał J., primary and Savin, Thierry, additional
- Published
- 2018
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19. Research Trends in Biological Fluid Dynamics
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Jung, Sunny, Staples, Anne E., Dabiri, John O., Marsden, Alison L., Prakash, Manu, Davis, Kristen A., Shadden, Shawn C., Savin, Thierry, Bourouiba, Lydia, and Sznitman, Josue
- Published
- 2015
20. Nonequilibrium thermodynamics of an interface
- Author
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Schweizer, Marco, primary, Öttinger, Hans Christian, additional, and Savin, Thierry, additional
- Published
- 2016
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21. Pressure-driven occlusive flow of a confined red blood cell
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Savin, Thierry, primary, Bandi, M. M., additional, and Mahadevan, L., additional
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- 2016
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22. Recent advances in the biomimicry of structural colours
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Dumanli, Ahu Gümrah, primary and Savin, Thierry, additional
- Published
- 2016
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23. Multiple particle tracking to assess the microstructure of biological fluids
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Patrick S. Doyle., Massachusetts Institute of Technology. Dept. of Chemical Engineering., Savin, Thierry, Ph. D. Massachusetts Institute of Technology, Patrick S. Doyle., Massachusetts Institute of Technology. Dept. of Chemical Engineering., and Savin, Thierry, Ph. D. Massachusetts Institute of Technology
- Abstract
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Chemical Engineering, 2006., This electronic version was submitted by the student author. The certified thesis is available in the Institute Archives and Special Collections., Includes bibliographical references (p. [137]-143)., Tracking the Brownian motion of colloids was first used about a hundred years ago to demonstrate the molecular nature of matter. Today's colloidal scientists perform particle tracking experiments to assess the structural and mechanical properties of complex materials at a micron length scale. Indeed, the dynamics of micron sized probe particles embedded in a material can be related to the local mechanical response of the system. This probing technique, called microrheology, has received much interest in the last few decades due to the importance of a materials local properties in its function and its macro-scale characteristics. These new assessments are especially relevant in soft matter sciences such as biophysics. Video microscopy particle tracking is an easy technique to implement experimentally. Movies of the fluctuating particles in a sample are recorded and analyzed off-line using custom algorithms. For this reason, it is widely used in studies of soft matter properties and in fluid dynamics. However, behind this apparent simplicity lie a number of subtle limitations that can alter significantly the validity of the measurements. The focus of the parts of this thesis is an exhaustive characterization of the errors incurred in the standard video microscopy particle tracking setup., (cont.) Detailed understanding of these errors led to new methods to circumvent some of the intrinsic limitations. The trajectories extracted from particle tracking are used to compute the means-squared displacement that characterizes the dynamics of the probe particles. This measurement suffers from two kinds of limitations: the finite spatial resolution in the particle localization and statistical uncertainties. The source of localization errors was separated into two separate contributions. A "static error" arises in the position measurements of immobilized particles. A "dynamic error" comes from the particle motion during the finite exposure time that is required for visualization. We calculated the propagation of these errors on the mean-squared displacement and examined the impact of our analysis on theoretical model fluids used in biorheology. These theoretical predictions were verified for purely viscous fluids using simulations and a multiple particle tracking technique performed with video microscopy. We showed that the static contribution could be confidently eling the sampling design, we derived estimators for the mean and variance of particle's dynamics that are independent, under well-efined conditions, of the peculiar statistics of the measurement output., (cont.) These estimators serve to quantify a material heterogeneity. Having gained a full characterization of the technique, we applied video multiple particle tracking to study a complex time-evolving system of self-assembling peptides. This material undergoes a transition from a purely viscous solution to an elastic hydrogel through the molecular assembly of the peptides into a fibrous network. We used the oligo-peptide KFE8 as a model self-assembling peptide and assessed the dependency of the gelation kinetics with the pH of the solution. We were able to develop a theoretical model for this dependency by using the Derjaguin-Landau-Verwey-Overbeek (DLVO) theory for the interaction between the peptides., by Thierry Savin., Ph.D.
- Published
- 2007
24. Thermodynamic formulation of flowing soft matter with transient forces
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Savin, Thierry, primary, Briels, Wim J., additional, and Öttinger, Hans Christian, additional
- Published
- 2012
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25. A method for tensile tests of biological tissues at the mesoscale
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Savin, Thierry, primary, Shyer, Amy E., additional, and Mahadevan, L., additional
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- 2012
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26. La morphogenèse de l’enroulement intestinal
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Savin, Thierry, primary
- Published
- 2011
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27. Using Mesoscopic Models to Design Strong and Tough Biomimetic Polymer Networks
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Salib, Isaac G., primary, Kolmakov, German V., additional, Bucior, Benjamin J., additional, Peleg, Orit, additional, Kröger, Martin, additional, Savin, Thierry, additional, Vogel, Viola, additional, Matyjaszewski, Krzysztof, additional, and Balazs, Anna C., additional
- Published
- 2011
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28. The Mechanism of Gut Loops Morphogenesis
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Savin, Thierry, primary
- Published
- 2011
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29. Stick-Slip Motion of a Red Blood Cell in a Capillary
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Savin, Thierry, primary and Mahadevan, L., additional
- Published
- 2009
- Full Text
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30. A rational approach to noise discrimination in video microscopy particle tracking
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Savin, Thierry, primary, Spicer, Patrick T., additional, and Doyle, Patrick S., additional
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- 2008
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31. Statistical and sampling issues when using multiple particle tracking
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Savin, Thierry, primary and Doyle, Patrick S., additional
- Published
- 2007
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32. Electrostatically tuned rate of peptide self-assembly resolved by multiple particle tracking
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Savin, Thierry, primary and Doyle, Patrick S., additional
- Published
- 2007
- Full Text
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33. Role of a finite exposure time on measuring an elastic modulus using microrheology
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Savin, Thierry, primary and Doyle, Patrick S., additional
- Published
- 2005
- Full Text
- View/download PDF
34. Percutaneous transluminal balloon valvuloplasty of adult aortic stenosis: Report of 92 cases
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Cribier, Alain, Savin, Thierry, Berland, Jacques, Rocha, Paulo, Mechmeche, Rachid, Saoudi, Nadir, Behar, Patrick, and Letac, Brice
- Abstract
Percutaneous transluminal balloon valvuloplasty was attempted in 92 adult patients with severe calcific aortic stenosis. The mean age was 75 ± 11 years (range 38 to 91) and 35 patients were more than 80 years old. Most of the patients were severely disabled; 66 were in New York Heart Association functional class III or IV, 27 had syncopal attacks and 21 had severe angina pectoris. Because of unacceptably high surgical risk or contraindication to thoracic surgery, 42 patients could not be considered for valve replacement. Other patients either were in a category of high operative risk or refused the surgical intervention.
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- 1987
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35. Approaches for microfluidics-enabled, bacterial, single-cell synthetic biology
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Moschner, Camillo, Savin, Thierry, and Haseloff, Jim
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Synthetic Biology ,microfluidics ,single-cell assays ,high-throughput experimentation ,2-photon polymerisation - Abstract
Synthetic biology, or biological engineering, deals with the rational, forward engineering of biological systems for useful purposes. In particular the subfield of biocomputing, i.e. the engineering of cell behaviour, has seen tremendous interest in applications ranging from medicine (e.g. living anti-cancer therapeutics) to the transportation industry (e.g. antifouling agent-producing bacteria living on submerged hulls of ships). In these complex environments, engineered cells' success or failure is defined by their individual as well as collective behaviours over long periods of time. Therefore, for successful biocomputing of living cells it is crucial to design, build and test engineered cells at single-cell resolution, with time-dependent behaviour in mind. This is possible through microfluidics-enhanced time-lapse imaging, specifically a microfluidics geometry called "Mother Machine". A Mother Machine microfluidic device (MFD) consists of a simple feeding lane through which cell medium flows, with perpendicularly connected cell trapping chambers, called trenches. This has previously been used to study wild-type or minimally-modified bacteria for mostly fundamental microbiology studies. In this thesis, I present my work on the adaptation of Mother Machine MFDs for biological engineering, and in particular biocomputing. For this purpose I have been using synthetic/ molecular biology, microfabrication, microfluidics, laboratory automation and programming approaches. Digital records, including programmes, design files and sequence maps, can be found on my PhD thesis GitHub repository (github.com/BioCam/PhD_thesis_cm967). Chapter 1 introduces the field of synthetic biology to a broad audience, presents my work on facilitating the biological engineering design process, and gives a background on biocomputing studies that leveraged microfluidics. Next, I introduce the detailed process for a Mother Machine-based synthetic biology experiment in Chapter 2. This acts as a case study of the motivations and limitations that existed at the beginning of my PhD. By testing three simple genetic circuits, which exert varying levels of energy demands on their host, I showcase the unique insights into engineered cells that microfluidics-enhanced, single-cell, time-lapse imaging offers. This work concluded that there are at least three precedence constraints for Mother Machine-enhanced synthetic biology that required overcoming for the field to advance. These are (1) problems with Mother Machine geometry-based limitations of retaining and efficiently supplying nutrients to cells with burdened, morphologically-changed phenotypes; (2) a sample/genotype throughput problem of only being able to test one sample in the same Mother Machine; and (3) the difficulty of preparing large numbers of samples at both the build and test stage in an automated, dynamic, low-cost manner. The aim of this thesis is to develop engineering solutions to these three precedence constraints. In Chapter 3, I address constraint #1. I discuss microfabrication techniques for the construction of Mother Machines with geometries that facilitate studying of burdened, morphologically-changed cells. I demonstrate important limitations with traditional UV photolithography, and present a novel hybrid 2-photon polymerisation (2PP)/UV photolithography microfabrication technology. In the following two chapters I examine two separate approaches addressing constraint #2. Though a Mother Machine can host up to millions of trenches which host individual cells, the sample number defined by unique genotypes is restricted to one due to limitations of how cells have to be loaded into trenches. This means that Mother Machine microfabrication defines trench throughput but sample throughput has to be increased in alternative ways. In Chapter 4, I explore the idea of rapidly increasing sample throughput through poolsynthesised libraries, screening them inside the MFD, and selecting cells with desired phenotypes through light-induced/optogenetic resistance to antibiotics. I present the work I have done towards this goal, and discuss serious limitations with existing optogenetic systems. To overcome these restrictions I designed a novel system with increased predictability In Chapter 5, in situ genotyping and holistic phenotype-genotype mapping of defined genetic libraries is discussed. I have investigated 5 different genotyping techniques before identifying fluorescent in situ hybridisation (FISH) as the most promising method. However, traditional FISH is severely limited in its maximal throughput due to cost, time and experimental complexity. I invented a novel, quencher-enhanced FISH technology that resolves these issues and present the proof-of-concept of this approach for Mother Machine-based, sample multiplexed experiments. In Chapter 6, I address constraint #3 by developing a low-cost, high-throughput lab automation pipeline, called "iBioFoundry" which facilitates the generation and experiment preparation of genetic circuits, with an emphasis on FISH-barcode integration. I established a series of programming algorithms that focus on dynamic automation and adaptability - two often overlooked paradigms in the field. Finally, I automated a collaborator's complex, 384-well experiment to highlight the advanced factorial design capabilities of the iBioFoundry.
- Published
- 2023
- Full Text
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36. Thermodynamic formulation of flowing soft matter with transient forces
- Author
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Savin, Thierry, Briels, Wim, Öttinger, Hans, Savin, Thierry, Briels, Wim, and Öttinger, Hans
- Abstract
The Responsive Particle Dynamics model is a very efficient method to account for the transient forces present in complex fluids, such as solutions of entangled polymers. This coarse-grained model considers a solution of particles that are made of a core and a corona. The cores typically interact through conservative interactions, while the coronae transiently penetrate each other to form short-lived temporary interactions, typically of entropic origin. In this study, we reformulate the resulting rheological model within the general framework of nonequilibrium thermodynamics called General Equation for the Nonequilibrium Reversible-Irreversible Coupling. This allows us to determine the consistency of the model, from a mechanistic and thermodynamic point of view, and to isolate the reversible and irreversible contributions to the dynamics of the model system
37. PERCUTANEOUS TRANSLUMINAL VALVULOPLASTY OF ACQUIRED AORTIC STENOSIS IN ELDERLY PATIENTS: AN ALTERNATIVE TO VALVE REPLACEMENT?
- Author
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Cribier, Alain, primary, Saoudi, Nadir, additional, Berland, Jacques, additional, Savin, Thierry, additional, Rocha, Paulo, additional, and Letac, Brice, additional
- Published
- 1986
- Full Text
- View/download PDF
38. Development of a novel micropipette aspiration-based force sensing technique to measure single cell sliding friction
- Author
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Bin Zaidon, Ahmad Zuheir and Savin, Thierry
- Subjects
biomechanics ,cellular tribology ,microtribology ,biosensor ,cellular biomechanics - Abstract
In numerous biological scenarios the motion of cells is tangential to the surface of contact such as in extravasation of leucocytes, blood flow regulation, and cell migration. In these cases, adhesion molecules on the cells form bonds with the substrate upon contact and when the cells propagate, the bonds are ruptured at an angle sustained by the cells' curvature. The presence of tangential force component (or the sliding friction) and the recruitments of auxiliary stress-dependent ligands at the adhesion site mean conventional cell detachment model is not adequate to explain the rupture mechanics of a sliding cell. Thus, we propose an instrument based on the micropipette aspiration technique to solve this problem. In this setup, a highly sensitive friction force sensor is made out of a long, thin, and hollow micropipette that deflects as a function of the tangential force experienced by a cell, aspirated at the tip, when rubbed against a moving substrate. Similarly, the substrate is connected to a normal force sensor that detects the perpendicular force acting on the cell by the surface during sliding. This dual force sensors setup allows direct measurements of all forces experienced by the moving cell to be gathered in real time. Separation between force sensors that monitors the friction and the normal force also allows the sensitivities of the sensors to be tuned independently. To prove the reliability of this device, we analyse the sliding of a glass bead against three different surface materials across multiple initial normal force values. Experiments are also performed across various sliding speeds and directionalities. The effect of varying load, speed and directionality are compared to similar meso- and nanoscale experiments and discussed. It is discovered that micro-friction has dependency on asperity properties that are intermediary to meso- and nanoscale experiments. Following that, experiments are performed with red blood cells, to demonstrate the first attempt of the device to measure bio-friction at single cell level. To supplement the sliding results, tactile experiment where the cells are detached perpendicular to the surface is carried out, and the rupture force is compared to that during sliding. It is found that the rupture force is indeed smaller in the presence of tangential force (during sliding). This provide novel experimental insight into quantitative values of bond-tilted rupture mechanics that can potentially be adopted in developing models that are more realistic and biologically relevant to cell detachment and bond rupture.
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- 2022
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39. Describing motions in biological tissues : a continuum active model and improving measurements
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Bogdan, Michal and Savin, Thierry
- Subjects
610.28 ,active fluids ,tissue invasion ,metastasis ,fingering instabilities ,Brownian motion ,measurement errors ,motion blur - Abstract
Motions in biological tissues strongly influence their properties and are crucial for their functions. This is true starting from the scale of single molecules, all the way up to the scale of entire tissues. One of the key properties distinguishing motions in living systems from those in dead matter is activity: using chemical energy to generate self-propulsion. Effective theoretical, physics-based models are necessary both to interpret the rich new experimental observations in the field of biological motions, and to properly account for the inherent errors of the experimental methods. In this work we study models related to motion both on the level of tissues and individual molecules. One of our models is driven by the observation that many growing tissues form multicellular protrusions at their edges. It is not fully understood how these are initiated, therefore we propose a minimal continuum physical model to suggest a possible mechanism. We apply our model to a growing circular tumour. We employ our approach to understand how activity affects the tumour’s dynamics and the tendency to form “fingers” at its boundary. This approach rests on just four key biophysical parameters and we can estimate them based on experiments described in the literature. Our modelling of a tumour is experimentally well justified and analytically solvable in many systems. It is, to the best of our knowledge, the first analytical description of tumour interface dynamics incorporating the activity of the tumour bulk. We can explain the propensity of tissues to fingering instabilities, as conditioned by the magnitude of active traction and the growth kinetics. We are also able to derive predictions for the tumour size at the onset of metastasis, and predictions for the number of subsequent invasive fingers. Microscopy-based techniques are essential for observing biological motions at all aforementioned length scales. Brownian particle videotracking is one example of such a technique. In the second part of this thesis, we apply physics-based theory to understand inherent errors and limitations of this method. Using analytic solutions and simulations, we show the effects of errors in particle videotracking on recovering energy landscapes from the distributions of Brownian particles. We point out mechanisms that result in nontrivial systematic biases in the measurements.
- Published
- 2019
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40. A magnetically actuated, optically sensed tensile testing method for mechanical characterization of soft biological tissues
- Author
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Luca Rosalia, Adrien Hallou, Laurence Cochrane, Thierry Savin, Rosalia, Luca [0000-0002-7214-7859], Hallou, Adrien [0000-0002-3162-7848], Cochrane, Laurence [0000-0003-3573-0962], Savin, Thierry [0000-0002-3956-7077], and Apollo - University of Cambridge Repository
- Subjects
Mice ,Multidisciplinary ,Elastomers ,Muscles ,Tensile Strength ,Animals ,Reproducibility of Results ,Stress, Mechanical ,Models, Biological ,Biomechanical Phenomena - Abstract
Mechanical properties of soft biological tissues play a key role in their normal physiology, contributing to their formation during development, maintenance and repair during adult homeostasis, and driving diseases such as cancer. Mechanics has been proposed to exert its effect by impacting cells fate decisions and cell behaviours including proliferation, differentiation and motility, amongst others. However, despite its critical relevance, a comprehensive analysis of the biomechanics of soft biological tissues is still lacking due to the limitations of the existing characterisation tools. In this article, we describe the development of a device for uniaxial tensile testing of small samples of epithelial and connective tissues, based on the closed-loop interaction between an electromagnetic force actuator and an optical strain sensor. First, we validate the device with synthetic elastomers of known mechanical properties and compare its performance with conventional tensile testing methods; then, we characterise the mechanical properties of the squamous epithelium of the mouse oesophagus along with its supporting connective tissue and underlying muscle in controlled environmental conditions. Through an analysis of strain-stress curves, we demonstrate that the whole oesophagus behaves as a trilayered composite material, whose overall mechanical response depends on the properties of each of its tissue layers. Overall, the proposed setup enables measurements of the mechanical properties of soft biological tissues with unprecedented reliability and precision, and offers an ideal platform for future instrument developments.
- Published
- 2023
- Full Text
- View/download PDF
41. Solution fibre spinning technique for the fabrication of tuneable decellularised matrix-laden fibres and fibrous micromembranes
- Author
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Elisabeth L. Gill, Yan Yan Shery Huang, Francesco Simone Ruggeri, Iek Man Lei, Simon C. Satchell, Natasha S. Lewis, Tuomas P. J. Knowles, Jack Tuffin, Zhaoying Li, Luai Huleihel, Stephen F. Badylak, Gavin I. Welsh, Thierry Savin, Moin A. Saleem, Lei, Iek Man [0000-0002-6337-1592], Ruggeri, Francesco [0000-0002-1232-1907], Savin, Thierry [0000-0002-3956-7077], Knowles, Tuomas [0000-0002-7879-0140], Huang, Shery [0000-0003-2619-730X], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Scaffold ,Materials science ,Swine ,Bristol Heart Institute ,Nanofibers ,Biomedical Engineering ,02 engineering and technology ,Matrix (biology) ,Biochemistry ,Fibre ,Biomaterials ,Extracellular matrix ,03 medical and health sciences ,Tissue engineering ,Elastic Modulus ,Tensile Strength ,Spectroscopy, Fourier Transform Infrared ,Animals ,Humans ,Molecular Biology ,Cells, Cultured ,Membranes ,Tissue Engineering ,Electrospinning ,biology ,Podocytes ,In vitro models ,General Medicine ,Elements ,021001 nanoscience & nanotechnology ,Membrane stiffness ,Solutions ,Fibronectin ,030104 developmental biology ,Membrane ,biology.protein ,Biophysics ,Stress, Mechanical ,0210 nano-technology ,Biotechnology ,Biofabrication - Abstract
Recreating tissue-specific microenvironments of the extracellular matrix (ECM) in vitro is of broad interest for the fields of tissue engineering and organ-on-a-chip. Here, we present biofunctional ECM protein fibres and suspended membranes, with tuneable biochemical, mechanical and topographical properties. This soft and entirely biologic membrane scaffold, formed by micro-nano-fibres using low voltage electrospinning, displays three unique characteristics for potential cell culture applications: high-content of key ECM proteins, single-layered mesh membrane, and flexibility for in situ integration into a range of device setups. Extracellular matrix (ECM) powder derived from urinary bladder, was used to fabricate the ECM-laden fibres and membranes. The highest ECM concentration in the dry protein fibre was 50 wt%, with the rest consisting of gelatin. Key ECM proteins, including collagen IV, laminin, and fibronectin, were shown to be preserved post the biofabrication process. The single fibre tensile Young’s modulus can be tuned for over two orders of magnitude between ∼600 kPa and 50 MPa depending on the ECM content. Combining the fibre mesh printing with 3D printed or microfabricated structures, culture devices were constructed for endothelial layer formation, and a trans-membrane co-culture formed by glomerular cell types of podocytes and glomerular endothelial cells, demonstrating feasibility of the membrane culture. Our cell culture observation points to the importance of membrane mechanical property and re-modelling ability as a factor for soft membrane-based cell cultures. The ECM-laden fibres and membranes presented here would see potential applications in in vitro assays, and tailoring structure and biological functions of tissue engineering scaffolds. Statement of Significance Recreating tissue-specific microenvironments of the extracellular matrix (ECM) is of broad interest for the fields of tissue engineering and organ-on-a-chip. Both the biochemical and biophysical signatures of the engineered ECM interplay to affect cell response. Currently, there are limited biomaterials processing methods which allow to design ECM membrane properties flexibly and rapidly. Solvents and additives used in many existing processes also induced unwanted ECM protein degradation and toxic residues. This paper presents a solution fibre spinning technique, where careful selection of the solution combination led to well-preserved ECM proteins with tuneable composition. This technique also provides a highly versatile approach to fabricate ECM fibres and membranes, leading to designable fibre Young’s modulus for over two orders of magnitude.
- Published
- 2018
- Full Text
- View/download PDF
42. A physical approach to model occlusions in the retinal microvasculature
- Author
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Thierry Savin, O Fleck, Savin, Thierry [0000-0002-3956-7077], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Bridging (networking) ,Retinal Artery Occlusion ,Computer science ,Physical approach ,Microfluidics ,01 natural sciences ,Microcirculation ,03 medical and health sciences ,chemistry.chemical_compound ,Particle dynamics ,0103 physical sciences ,Occlusion ,Retinal Vein Occlusion ,Humans ,010306 general physics ,Probabilistic logic ,Retinal Vessels ,Retinal ,Models, Theoretical ,Cambridge Ophthalmological Symposium ,Ophthalmology ,030104 developmental biology ,chemistry ,Regional Blood Flow ,Microvessels ,Biological system - Abstract
Blood occlusions in the retinal microvasculature contribute to the pathology of many disease states within the eye. These events can cause haemorrhaging and retinal detachment, leading to a loss of vision in the affected patient. Here, we present a physical approach to characterising the collective cell dynamics leading to plug formation, through the use of a bespoke microfluidic device, and through the derivation of a probabilistic model. Our microfluidic device is based on a filtration design that can tune the particle volume fraction of a flowing suspension within a conduit, with sizes similar to arterioles. This allows us to control and reproduce an occlusive event. The formation of the occlusion can be examined through the extracted motion of particles within the channel, which enables the assessment of individual and collective particle dynamics in the time leading to the clogging event. In particular, we observe that at the onset of the occlusion, particles form an arch bridging the channel walls. The data presented here inform the development of our mathematical model, which captures the essential factors promoting occlusions, and notably highlights the central role of adhesion in these processes. Both the physical and probabilistic models rely on significant approximations, and future investigation will seek to assess these approximations, including the deformability and complex flow profiles of the blood constituents. However, we anticipate that the general mechanisms of occlusion may be elucidated from these simple models. As microvascular flows in the eye can now be measured in vivo and non-invasively with single cell resolution, our model will also be compared to the pathophysiological characteristics of the human microcirculation.
- Published
- 2018
- Full Text
- View/download PDF
43. Errors in Energy Landscapes Measured with Particle Tracking
- Author
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Thierry Savin, Michal Bogdan, Savin, Thierry [0000-0002-3956-7077], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Physics ,Time Factors ,Optical Tweezers ,Motion blur ,Biophysics ,Energy landscape ,FOS: Physical sciences ,Condensed Matter - Soft Condensed Matter ,Tracking (particle physics) ,01 natural sciences ,Maxima and minima ,03 medical and health sciences ,030104 developmental biology ,Video tracking ,0103 physical sciences ,Brownian dynamics ,Soft Condensed Matter (cond-mat.soft) ,Thermodynamics ,Molecular Machines, Motors, and Nanoscale Biophysics ,Noise (video) ,Statistical physics ,010306 general physics ,Brownian motion - Abstract
Tracking Brownian particles is often employed to map the energy landscape they explore. Such measurements have been exploited to study many biological processes and interactions in soft materials. Yet, video tracking is irremediably contaminated by localization errors originating from two imaging artifacts: the "static" errors come from signal noise, and the "dynamic" errors arise from the motion blur due to finite frame acquisition time. We show that these errors result in systematic and non-trivial biases in the measured energy landscapes. We derive a relationship between the true and the measured potential that elucidates, among other aberrations, the presence of false double-well minima in the apparent potentials reported in recent studies. We further assess several canonical trapping and pair-interaction potentials, by using our analytically derived results and Brownian dynamics simulations. In particular, we show that the apparent spring stiffness of harmonic potentials (such as optical traps) is increased by dynamic errors, but decreased by static errors. Our formula allows for the development of efficient corrections schemes, which we also present in this paper., Comment: 10 pages, 6 figures
- Published
- 2017
44. Pressure-driven occlusive flow of a confined red blood cell
- Author
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Mahesh Bandi, Thierry Savin, Lakshminarayanan Mahadevan, Savin, Thierry [0000-0002-3956-7077], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,Erythrocytes ,Capillary action ,Physics::Medical Physics ,Blood viscosity ,02 engineering and technology ,Models, Biological ,Quantitative Biology::Cell Behavior ,Microcirculation ,Physics::Fluid Dynamics ,03 medical and health sciences ,Optics ,medicine ,Cell Adhesion ,Pressure ,Pressure gradient ,Pressure drop ,business.industry ,Chemistry ,General Chemistry ,Radius ,Mechanics ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,Red blood cell ,030104 developmental biology ,medicine.anatomical_structure ,Hemorheology ,Hydrodynamics ,0210 nano-technology ,business - Abstract
When red blood cells (RBCs) move through narrow capillaries in the microcirculation, they deform as they flow. In pathophysiological processes such as sickle cell disease and malaria, RBC motion and flow are severely restricted. To understand this threshold of occlusion, we use a combination of experiment and theory to study the motion of a single swollen RBC through a narrow glass capillary of varying inner diameter. By tracking the movement of the squeezed cell as it is driven by a controlled pressure drop, we measure the RBC velocity as a function of the pressure gradient as well as the local capillary diameter, and find that the effective blood viscosity in this regime increases with both decreasing RBC velocity and tube radius by following a power-law that depends upon the length of the confined cell. Our observations are consistent with a simple elasto-hydrodynamic model and highlight the role of lateral confinement in the occluded pressure-driven slow flow of soft confined objects.
- Published
- 2016
45. Recent advances in the biomimicry of structural colours
- Author
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Ahu Gümrah Dumanlı, Thierry Savin, Savin, Thierry [0000-0002-3956-7077], and Apollo - University of Cambridge Repository
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Physics ,Optics and Photonics ,Light ,Molecular Structure ,Polymers ,Surface Properties ,Color ,Nanotechnology ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Silicon Dioxide ,01 natural sciences ,0104 chemical sciences ,Iridescence ,Nanostructures ,Biomimetic Materials ,Biomimetics ,Particle Size ,0210 nano-technology - Abstract
Nature has mastered the construction of nanostructures with well-defined macroscopic effects and purposes. Structural colouration is a visible consequence of the particular patterning of a reflecting surface with regular structures at submicron length scales. Structural colours usually appear bright, shiny, iridescent or with a metallic look, as a result of physical processes such as diffraction, interference, or scattering with a typically small dissipative loss. These features have recently attracted much research effort in materials science, chemistry, engineering and physics, in order to understand and produce structural colours. In these early stages of photonics, researchers facing an infinite array of possible colour-producing structures are heavily inspired by the elaborate architectures they find in nature. We review here the recent technological strategies employed to artificially mimic the structural colours found in nature, as well as some of their current and potential applications.
- Published
- 2016
- Full Text
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46. Brownian and Nonisothermal Effects in Nucleation Theory: Towards Systematic Multiscale Modeling
- Author
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Schweizer, Marco, Öttinger, Hans Christian, and Savin, Thierry
- Subjects
NUMERICAL SIMULATION AND MATHEMATICAL MODELING ,KEIMBILDUNG + PHASENUMWANDLUNG (WÄRMELEHRE) ,OBERFLÄCHEN + GRENZFLÄCHEN + BRUCHFLÄCHEN (PHYSIK VON MOLEKULARSYSTEMEN) ,NUCLEATION + PHASE CHANGE (THERMOPHYSICS) ,Physics ,MOLECULAR DYNAMICS (MOLECULAR PHYSICS) ,STOCHASTIC APPROXIMATION + MONTE CARLO METHODS (STOCHASTICS) ,STOCHASTISCHE APPROXIMATION + MONTE-CARLO-METHODEN (STOCHASTIK) ,NUMERISCHE SIMULATION UND MATHEMATISCHE MODELLRECHNUNG ,MOLEKULARE DYNAMIK (MOLEKÜLPHYSIK) ,SURFACES + INTERFACES + FRACTURE SURFACES (PHYSICS OF MOLECULAR SYSTEMS) ,ddc:530 - Published
- 2015
- Full Text
- View/download PDF
47. [Gut looping morphogenesis].
- Author
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Savin T
- Subjects
- Animals, Biophysical Phenomena physiology, Birds anatomy & histology, Birds embryology, Chick Embryo, Embryonic Development physiology, Humans, Mice, Models, Biological, Physical Phenomena, Body Patterning physiology, Intestines anatomy & histology, Intestines embryology, Morphogenesis physiology
- Published
- 2011
- Full Text
- View/download PDF
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