12 results on '"Sam C. P. Norris"'
Search Results
2. Cell-Taxi: Mesenchymal Cells Carry and Transport Clusters of Cancer Cells
- Author
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Jana Zarubova, Mohammad Mahdi Hasani‐Sadrabadi, Sam C. P. Norris, Fatemeh Sadat Majedi, Crystal Xiao, Andrea M. Kasko, and Song Li
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Biomaterials ,Cell Movement ,Neoplasms ,Cell Line, Tumor ,Humans ,General Materials Science ,Mesenchymal Stem Cells ,General Chemistry ,Stromal Cells ,Biotechnology - Abstract
Cell clusters that collectively migrate from primary tumors appear to be far more potent in forming distant metastases than single cancer cells. A better understanding of the collective cell migration phenomenon and the involvement of various cell types during this process is needed. Here, an in vitro platform based on inverted-pyramidal microwells to follow and quantify the collective migration of hundreds of tumor cell clusters at once is developed. These results indicate that mesenchymal stromal cells (MSCs) or cancer-associated fibroblasts (CAFs) in the heterotypic tumor cell clusters may facilitate metastatic dissemination by transporting low-motile cancer cells in a Rac-dependent manner and that extracellular vesicles secreted by mesenchymal cells only play a minor role in this process. Furthermore, in vivo studies show that cancer cell spheroids containing MSCs or CAFs have faster spreading rates. These findings highlight the active role of co-traveling stromal cells in the collective migration of tumor cell clusters and may help in developing better-targeted therapies.
- Published
- 2022
3. Cell‐Taxi: Mesenchymal Cells Carry and Transport Clusters of Cancer Cells (Small 50/2022)
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Jana Zarubova, Mohammad Mahdi Hasani‐Sadrabadi, Sam C. P. Norris, Fatemeh Sadat Majedi, Crystal Xiao, Andrea M. Kasko, and Song Li
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Biomaterials ,General Materials Science ,General Chemistry ,Biotechnology - Published
- 2022
4. Mechanically robust photodegradable gelatin hydrogels for 3D cell culture and in situ mechanical modification
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Andrea M. Kasko, Stephanie Delgado, and Sam C. P. Norris
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food.ingredient ,Polymers and Plastics ,Organic Chemistry ,technology, industry, and agriculture ,Biomaterial ,Bioengineering ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Biochemistry ,Gelatin ,0104 chemical sciences ,chemistry.chemical_compound ,3D cell culture ,food ,Isoelectric point ,chemistry ,Chemical engineering ,PEG ratio ,Self-healing hydrogels ,Methacrylamide ,0210 nano-technology ,Ethylene glycol - Abstract
Recent developments in photodegradable (PD) hydrogels have allowed researchers to study cell behavior in response to spatial and temporal changes to the extracellular environment. To date, most PD hydrogel systems have been composed of poly (ethylene glycol) (PEG) based macromers that crosslink via end-linking gelation. PEG-based hydrogels, however, are not optimal for three-dimension cell culture, as they neither allow for cellular proliferation nor restructuring of the matrix. Unlike PEG-based hydrogels, gelatin, a naturally derived material, contains enzymatically degradable sites and cell binding domains, making it an attractive biomaterial for three-dimensional cell culture. To this end, researchers have modified gelatin to contain methacrylamide groups (GelMA). This allows the gels to be chemically crosslinked, rendering them stable at physiological temperatures. A few groups have also reported the synthesis of PD gelatin, but the incorporation of photodegradable groups is hampered by poor conjugation efficiency and poor solubility, leading to insufficient mechanical properties. In this work, we develop a PD gelatin hydrogel system that is mechanically robust and can be easily produced in large quantities. Specifically, we chemically modify the gelatin with highly hydrophilic groups which, in turn, adjust the isoelectric point and charge density of the protein. This modification results in a highly soluble PD-gelatin that can be crosslinked into a gel and subsequently degraded with exposure to light. These PD-gelatin gels exhibit mechanical properties similar to GelMA gels, but with the extra ability to be spatially and temporally patterned with light. Photodegradation of the gels can be done either before cell seeding or in the presence of cells. We show that cells respond to both patterned structures and in situ softening of the network in 2D, while in situ softening in 3D does not affect morphology at the compositions and time scales investigated.
- Published
- 2019
5. Mesenchymal stem cells carry and transport clusters of cancer cells
- Author
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Andrea M. Kasko, Sam C. P. Norris, Mohammad Mahdi Hasani-Sadrabadi, Song Li, and Jana Zarubova
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Paracrine signalling ,Cell type ,medicine.anatomical_structure ,Stromal cell ,Chemistry ,Cell ,Cancer cell ,Mesenchymal stem cell ,medicine ,Spheroid ,medicine.disease ,Metastasis ,Cell biology - Abstract
Cell clusters that collectively migrate from primary tumors appear to be far more potent in forming distant metastases than single cancer cells. A better understanding of collective cell migration phenomenon and the involvement of different cell types during this process is needed. Here, we utilize a micropatterned surface composed of a thousand of low-adhesive microwells to screen motility of spheroids containing different cell types by analyzing their ability to move from the bottom to the top of the microwells. Mesenchymal stem cells (MSCs) spheroid migration was efficient in contrast to cancer cell only spheroids. In spheroids with both cell types mixed together, MSCs were able to carry the low-motile cancer cells during migration. As the percentage of MSCs increased in the spheroids, more migrating spheroids were detected. Extracellular vesicles secreted by MSCs also contributed to the pro-migratory effect exerted by MSCs. However, the transport of cancer cells was more efficient when MSCs were physically present in the cluster. Similar results were obtained when cell clusters were encapsulated within a micropatterned hydrogel, where collective migration was guided by micropatterned matrix stiffness. These results suggest that stromal cells facilitate the migration of cancer cell clusters, which is contrary to the general belief that malignant cells metastasize independently.SignificanceDuring metastasis, tumor cells may migrate as a cluster, which exhibit higher metastatic capacity compared to single cells. However, whether and how non-cancer cells contained in tumor cluster regulate it’s migration is not clear. Here, we utilize two unique approaches to study collective tumor cell migration in vitro: first, in low-adhesive microwells and second, in micropatterned hydrogels to analyze migration in 3D microenvironment. Our results indicate that MSCs in tumor cell clusters could play an important role in the dissemination of cancer cells by actively transporting low-motile cancer cells. In addition, MSC-released paracrine factors also increase the motility of tumor cells. These findings reveal a new mechanism of cancer cell migration and may lead to new approaches to suppress metastases.
- Published
- 2021
6. Photodegradable Polyacrylamide Gels for Dynamic Control of Cell Functions
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Sam C. P. Norris, Song Li, Andrea M. Kasko, and Jennifer Soto
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Polyacrylamide Hydrogel ,Materials science ,Surface Properties ,Polyacrylamide ,Acrylic Resins ,02 engineering and technology ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,Cell Adhesion ,Animals ,General Materials Science ,Particle Size ,Polyacrylamide gel electrophoresis ,Softening ,Cells, Cultured ,030304 developmental biology ,0303 health sciences ,Molecular Structure ,technology, industry, and agriculture ,Substrate (chemistry) ,Hydrogels ,021001 nanoscience & nanotechnology ,Photochemical Processes ,Actins ,Mice, Inbred C57BL ,chemistry ,Acrylamide ,Self-healing hydrogels ,Biophysics ,Adhesive ,0210 nano-technology - Abstract
Cross-linked polyacrylamide hydrogels are commonly used in biotechnology and cell culture applications due to advantageous properties, such as the precise control of material stiffness and the attachment of cell adhesive ligands. However, the chemical and physical properties of polyacrylamide gels cannot be altered once fabricated. Here, we develop a photodegradable polyacrylamide gel system that allows for a dynamic control of polyacrylamide gel stiffness with exposure to light. Photodegradable polyacrylamide hydrogel networks are produced by copolymerizing acrylamide and a photocleavable ortho-nitrobenzyl (o-NB) bis-acrylate cross-linker. When the hydrogels are exposed to light, the o-NB cross-links cleave and the stiffness of the photodegradable polyacrylamide gels decreases. Further examination of the effect of dynamic stiffness changes on cell behavior reveals that in situ softening of the culture substrate leads to changes in cell behavior that are not observed when cells are cultured on presoftened gels, indicating that both dynamic and static mechanical environments influence cell fate. Notably, we observe significant changes in nuclear localization of YAP and cytoskeletal organization after in situ softening; these changes further depend on the type and concentration of cell adhesive proteins attached to the gel surface. By incorporating the simplicity and well-established protocols of standard polyacrylamide gel fabrication with the dynamic control of photodegradable systems, we can enhance the capability of polyacrylamide gels, thereby enabling cell biologists and engineers to study more complex cellular behaviors that were previously inaccessible using regular polyacrylamide gels.
- Published
- 2021
7. Direct Gradient Photolithography of Photodegradable Hydrogels with Patterned Stiffness Control with Submicrometer Resolution
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Sam C. P. Norris, Peter Tseng, and Andrea M. Kasko
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Materials science ,technology, industry, and agriculture ,Biomedical Engineering ,Stiffness ,Nanotechnology ,macromolecular substances ,02 engineering and technology ,Substrate (printing) ,Orders of magnitude (numbers) ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,Grayscale ,Soft lithography ,0104 chemical sciences ,law.invention ,Biomaterials ,Matrix (mathematics) ,law ,Self-healing hydrogels ,medicine ,Photolithography ,medicine.symptom ,0210 nano-technology ,Biomedical engineering - Abstract
Cell response to matrix mechanics is well-known; however, the ability to spatially pattern matrix stiffness to a high degree of control has been difficult to attain. This study describes the use of maskless photolithography as a flexible process for direct, noncontact gradient patterning of photodegradable hydrogels with custom graphics. Any input gray scale image can be used to directly chart hydrogel cross-link density as a function of spatial position. Hydrogels can be patterned with submicron resolution, with length scales within a single substrate spanning several orders of magnitude. A quantitative relationship between input grayscale image pixel intensity and output gel stiffness is validated, allowing for direct gradient patterning. Such physical gradient hydrogel constructs are rapidly produced in a highly controlled fashion with measured stiffness ranges and length scales that are physiologically relevant. Mesenchymal stem cells cultured on these physical gradients matrices congregate and align orthogonal to the gradient direction along iso-degraded lines. This approach results in a robust and high-throughput platform to answer key questions about cell response in heterogeneous physical environments.
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- 2021
8. Stochastic model of randomly end-linked polymer network micro-regions
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Andrea M. Kasko, Sam C. P. Norris, Maria R. D'Orsogna, and Tom Chou
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Fabrication ,Materials science ,Polymers and Plastics ,Stochastic modelling ,FOS: Physical sciences ,Nanotechnology ,02 engineering and technology ,Condensed Matter - Soft Condensed Matter ,010402 general chemistry ,01 natural sciences ,Inorganic Chemistry ,parasitic diseases ,Materials Chemistry ,chemistry.chemical_classification ,Condensed Matter - Materials Science ,Polymer network ,Organic Chemistry ,technology, industry, and agriculture ,Materials Science (cond-mat.mtrl-sci) ,Polymer ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Polymerization ,chemistry ,Soft Condensed Matter (cond-mat.soft) ,0210 nano-technology - Abstract
Polymerization and formation of crosslinked polymer networks are important processes in manufacturing, materials fabrication, and in the case of hydrated polymer networks, synthesis of biomedical materials, drug delivery, and tissue engineering. While considerable research has been devoted to the modeling of polymer networks to determine averaged, mean-field, global properties, there are fewer studies that specifically examine the variance of the composition across "micro-regions" (composed of a large, but finite, number of polymer network strands) within the larger polymer network.Here, we mathematically model the stochastic formation of polymer networks comprised of linear homobifunctional network strands that undergo an end-linking gelation process. We introduce a master equation that describes the evolution of the probabilities of possible network micro-region configurations as a function of time and extent of reaction. We specifically focus on the dynamics of network formation and the statistical variability of the gel micro-regions, particularly at intermediate extents of reaction. We also consider possible annealing effects and study how cooperative binding between the two end-groups on a single network-strand affects network formation. Our results allow for a more detailed and thorough understanding of polymer network dynamics and variability of network properties., Comment: 16 pages, 9 figures
- Published
- 2019
- Full Text
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9. Raster image correlation spectroscopy as a novel tool to study interactions of macromolecules with nanofiber scaffolds
- Author
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Martin Hof, Evžen Amler, David Lukas, Sam C. P. Norris, Matej Buzgo, Radek Macháň, Martina Huranova, and Jana Humpolíčková
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Materials science ,Nanofibers ,Biomedical Engineering ,Nanotechnology ,02 engineering and technology ,Biochemistry ,Diffusion ,Biomaterials ,03 medical and health sciences ,chemistry.chemical_compound ,Molecule ,Diffusion (business) ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,Fluorescence recovery after photobleaching ,General Medicine ,021001 nanoscience & nanotechnology ,chemistry ,Nanofiber ,Self-healing hydrogels ,Biophysics ,Agarose ,0210 nano-technology ,Two-dimensional nuclear magnetic resonance spectroscopy ,Protein Binding ,Biotechnology ,Macromolecule - Abstract
Dynamic processes such as diffusion and binding/unbinding of macromolecules (e.g. growth factors or nutrients) are crucial parameters for the design and application of effective artificial tissue materials. Here, dynamics of selected macromolecules were studied in two different composite tissue engineering scaffolds containing an electrospun nanofiber mesh (polycaprolactone or hydrophobically plasma modified polyvinylalcohol–chitosan) encapsulated in agarose hydrogels by a conventional approach fluorescence recovery after photobleaching (FRAP) and a novel technique, raster image correlation spectroscopy (RICS). The two approaches are compared, and it is shown that FRAP is unable to determine processes occurring at low molecular concentrations, especially accurately separating binding/unbinding from diffusion, and its results depend on the concentration of the studied molecules. RICS measures processes of single molecules and, because of its multiple adjustable timescales, can distinguish whether diffusion or binding controls molecular movement and separates fast diffusion from slow transient binding. In addition, RICS provides a robust read-out parameter quantifying binding affinity. Finally, the combination of FRAP and RICS helps to characterize diffusion and binding of macromolecules in tested artificial tissues better, and therefore predicts the behavior of biologically active molecules in these materials for medical applications.
- Published
- 2011
10. Detection of Suspicious Mass on Structures by Acoustical Waves
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Sam C. P. Norris, J. Trnka, and P. Stoklasová
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Physics ,Frequency analysis ,Explosive material ,business.industry ,Mechanical Engineering ,Acoustics ,law.invention ,Pulse (physics) ,Interferometry ,Speckle pattern ,Lamb waves ,Optics ,Mechanics of Materials ,law ,Waveform ,Time domain ,business - Abstract
Analysis of scattered Lamb waves in thin plates and shells, with an added foreign mass on their surface, was performed. Waves were generated in a range of frequencies, up to 80 kHz, by an impact loading. The responses were detected by full-field and point-wise optical methods. Pulse holointerferometry and pulse electronic speckle patterns interferometry techniques were used to visualize the interaction of the Lamb waves with the added foreign mass. Double-channel laser vibrometry was used to record the velocity history within the proximity of the added foreign mass. It was shown that frequency analysis of the recorded waveforms was more convenient than time domain analysis when investigating the response in the thin-walled structures. The proposed method is applicable to search for suspicious masses (e.g. explosive devices) added to the structures.
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- 2011
11. Diffusion of Photoabsorbing Degradation Byproducts in Photodegradable Polymer Networks
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Tom Chou, Sam C. P. Norris, and Andrea M. Kasko
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chemistry.chemical_classification ,Materials science ,Polymers and Plastics ,Organic Chemistry ,02 engineering and technology ,Polymer ,Light attenuation ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,0104 chemical sciences ,Inorganic Chemistry ,chemistry ,Chemical engineering ,Scientific method ,Self-healing hydrogels ,Materials Chemistry ,Degradation (geology) ,Organic chemistry ,Diffusion (business) ,0210 nano-technology ,Material properties ,Photodegradation - Abstract
Photodegradation of crosslinked, hydrated polymer networks is an important lithographic process in the fabrication of structured biomaterials. In order to better understand the properties of materials fabricated using photodegradation, the process is mathematically modeled, paying special attention to how diffusible photoabsorbing species mediate the degradation of the polymer network. These light-absorbing species may significantly alter light attenuation; thus, understanding the spatial movement of these species is critical in developing a predictive model of photodegradation. Using a series of mass-action models, diffusion of absorbing species is shown to play a significant role in determining the final state of the photodegraded network. The predicted degree of degradation is significantly different when including the effects of diffusion than that predicted when neglecting diffusion. This model also explores degradation profiles that result from different experimental geometries. This model is the most accurate description to date of the relationship between experimental conditions and resulting photodegradation.
- Published
- 2017
12. Can OCT be sensitive to nanoscale structural alterations in biological tissue?
- Author
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Sam C. P. Norris, Capoglu Ilker R, Jeremy D. Rogers, Vadim Backman, Ji Yi, Allen Taflove, and Andrew J. Radosevich
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Length scale ,In situ ,Materials science ,Models, Biological ,Sensitivity and Specificity ,Imaging, Three-Dimensional ,Optics ,Optical coherence tomography ,Image Interpretation, Computer-Assisted ,medicine ,Animals ,Humans ,Computer Simulation ,Nanoscopic scale ,Image resolution ,Models, Statistical ,medicine.diagnostic_test ,business.industry ,Reproducibility of Results ,Atomic and Molecular Physics, and Optics ,Rats ,Correlation function (statistical mechanics) ,Research-Article ,Tomography ,business ,Tomography, Optical Coherence ,Ex vivo - Abstract
Exploration of nanoscale tissue structures is crucial in understanding biological processes. Although novel optical microscopy methods have been developed to probe cellular features beyond the diffraction limit, nanometer-scale quantification remains still inaccessible for in situ tissue. Here we demonstrate that, without actually resolving specific geometrical feature, OCT can be sensitive to tissue structural properties at the nanometer length scale. The statistical mass-density distribution in tissue is quantified by its autocorrelation function modeled by the Whittle-Mateŕn functional family. By measuring the wavelength-dependent backscattering coefficient μb(λ) and the scattering coefficient μs, we introduce a technique called inverse spectroscopic OCT (ISOCT) to quantify the mass-density correlation function. We find that the length scale of sensitivity of ISOCT ranges from ~30 to ~450 nm. Although these sub-diffractional length scales are below the spatial resolution of OCT and therefore not resolvable, they are nonetheless detectable. The sub-diffractional sensitivity is validated by 1) numerical simulations; 2) tissue phantom studies; and 3) ex vivo colon tissue measurements cross-validated by scanning electron microscopy (SEM). Finally, the 3D imaging capability of ISOCT is demonstrated with ex vivo rat buccal and human colon samples.
- Published
- 2013
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