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David Stopak

Bio: David Stopak is an academic researcher from University of North Carolina at Chapel Hill. The author has contributed to research in topics: Silicone rubber & Traction (orthopedics). The author has an hindex of 4, co-authored 4 publications receiving 2882 citations.

Papers
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Journal ArticleDOI
11 Apr 1980-Science
TL;DR: When tissue cells are cultured on very thin sheets of cross-linked silicone fluid, the traction forces the cells exert are made visible as elastic distortion and wrinkling of this substratum.
Abstract: When tissue cells are cultured on very thin sheets of cross-linked silicone fluid, the traction forces the cells exert are made visible as elastic distortion and wrinkling of this substratum. Around explants this pattern of wrinkling closely resembles the "center effects" long observed in plasma clots and traditionally attributed to dehydration shrinkage.

1,377 citations

Journal ArticleDOI
19 Mar 1981-Nature
TL;DR: It is proposed that this morphogenetic rearrangement of extracellular matrices is the primary function of fibroblast traction and explains its excessive strength.
Abstract: To make visible the traction forces exerted by individual cells, we have previously developed a method of culturing them on thin distortable sheets of silicone rubber1. We have now used this method to compare the forces exerted by various differentiated cell types and have examined the effects of cellular traction on re-precipitated collagen matrices. We find that the strength of cellular traction differs greatly between cell types and this traction is paradoxically weakest in the most mobile and invasive cells (leukocytes and nerve growth cones). Untransformed fibroblasts exert forces very much larger than those actually needed for locomotion. This strong traction distorts collagen gels dramatically, creating patterns similar to tendons and organ capsules. We propose that this morphogenetic rearrangement of extracellular matrices is the primary function of fibroblast traction and explains its excessive strength.

875 citations

Journal ArticleDOI
TL;DR: It is found that the force fibroblasts use to propel themselves (traction) is sufficiently strong to distort collagen gels and to form patterns of tension, compression, and alignment similar to the wrinkling patterns previously observed on silicone rubber.

614 citations

Journal ArticleDOI
TL;DR: It is proposed that an equivalent mechanical instability, occurring during the embryonic development of this skin, could be the cause not only of the clumping of dermal fibroblasts to form the feather papillae, but also of the alignment of collagen fibres into the characteristic polygonal network of fibre bundles - which interconnect these Papillae and which presage the subsequent pattern of the dermal muscles serving to control feather movements.
Abstract: We have studied the generation of spatial patterns created by mechanical (rather than chemical) instabilities. When dissociated fibroblasts are suspended in a gel of reprecipitated collagen, and the contraction of the gel as a whole is physically restrained by attachment of its margin to a glass fibre meshwork, then the effect of the fibroblasts' traction is to break up the cell-matrix mixture into a series of clumps or aggregations of cells and compressed matrix. These aggregations are interconnected by linear tracts of collagen fibres aligned under the tensile stress exerted by fibroblast traction. The patterns generated by this mechanical instability vary depending upon cell population density and other factors. Over a certain range of cell concentrations, this mechanical instability yields geometric patterns which resemble but are usually much less regular than the patterns which develop normally in the dermis of developing bird skin. We propose that an equivalent mechanical instability, occurring during the embryonic development of this skin, could be the cause not only of the clumping of dermal fibroblasts to form the feather papillae, but also of the alignment of collagen fibres into the characteristic polygonal network of fibre bundles - which interconnect these papillae and which presage the subsequent pattern of the dermal muscles serving to control feather movements. More generally, we suggest that this type of mechanical instability can serve the morphogenetic functions for which Turing's chemical instability and other reaction-diffusion systems have been proposed. Mechanical instabilities can create physical structures directly, in one step, in contrast to the two or more steps which would be required if positional information first had to be specified by chemical gradients and then only secondarily implemented in physical form. In addition, physical forces can act more quickly and at much longer range than can diffusing chemicals and can generate a greater range of possible geometries than is possible using gradients of scalar properties. In cases (such as chondrogenesis) where cell differentiation is influenced by the local population density of cells and extracellular matrix, the physical patterns of force and distortion within this extracellular matrix should even be able to accomplish the spatial control of differentiation, usually attributed to diffusible 'morphogens'.

127 citations


Cited by
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Journal ArticleDOI
18 Nov 2005-Science
TL;DR: An understanding of how tissue cells—including fibroblasts, myocytes, neurons, and other cell types—sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels with which elasticity can be tuned to approximate that of tissues.
Abstract: Normal tissue cells are generally not viable when suspended in a fluid and are therefore said to be anchorage dependent. Such cells must adhere to a solid, but a solid can be as rigid as glass or softer than a baby's skin. The behavior of some cells on soft materials is characteristic of important phenotypes; for example, cell growth on soft agar gels is used to identify cancer cells. However, an understanding of how tissue cells-including fibroblasts, myocytes, neurons, and other cell types-sense matrix stiffness is just emerging with quantitative studies of cells adhering to gels (or to other cells) with which elasticity can be tuned to approximate that of tissues. Key roles in molecular pathways are played by adhesion complexes and the actinmyosin cytoskeleton, whose contractile forces are transmitted through transcellular structures. The feedback of local matrix stiffness on cell state likely has important implications for development, differentiation, disease, and regeneration.

5,889 citations

Journal ArticleDOI
09 Feb 1996-Cell
TL;DR: The authors are grateful for financial support from the National Institutes of Health (grants GM23244 and GM53905), and to very helpful comments on the manuscript from Elliot Elson, Vlodya Gelfand, Paul Matsudaira, Julie Theriot, and Sally Zigmond.

3,973 citations

Journal ArticleDOI
TL;DR: It is clear that the understanding of the myofibroblast — its origins, functions and molecular regulation — will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.
Abstract: During the past 20 years, it has become generally accepted that the modulation of fibroblastic cells towards the myofibroblastic phenotype, with acquisition of specialized contractile features, is essential for connective-tissue remodelling during normal and pathological wound healing. Yet the myofibroblast still remains one of the most enigmatic of cells, not least owing to its transient appearance in association with connective-tissue injury and to the difficulties in establishing its role in the production of tissue contracture. It is clear that our understanding of the myofibroblast its origins, functions and molecular regulation will have a profound influence on the future effectiveness not only of tissue engineering but also of regenerative medicine generally.

3,836 citations

Journal ArticleDOI
TL;DR: It is discovered that changes in tissue rigidity and strain could play an important controlling role in a number of normal and pathological processes involving cell locomotion, including morphogenesis, the immune response, and wound healing.

3,189 citations

Journal ArticleDOI
TL;DR: The ability of cells to survey the mechanical properties of their surrounding environment is demonstrated and the possible involvement of both protein tyrosine phosphorylation and myosin-generated cortical forces in this process is suggested.
Abstract: Responses of cells to mechanical properties of the adhesion substrate were examined by culturing normal rat kidney epithelial and 3T3 fibroblastic cells on a collagen-coated polyacrylamide substrate that allows the flexibility to be varied while maintaining a constant chemical environment. Compared with cells on rigid substrates, those on flexible substrates showed reduced spreading and increased rates of motility or lamellipodial activity. Microinjection of fluorescent vinculin indicated that focal adhesions on flexible substrates were irregularly shaped and highly dynamic whereas those on firm substrates had a normal morphology and were much more stable. Cells on flexible substrates also contained a reduced amount of phosphotyrosine at adhesion sites. Treatment of these cells with phenylarsine oxide, a tyrosine phosphatase inhibitor, induced the formation of normal, stable focal adhesions similar to those on firm substrates. Conversely, treatment of cells on firm substrates with myosin inhibitors 2,3-butanedione monoxime or KT5926 caused the reduction of both vinculin and phosphotyrosine at adhesion sites. These results demonstrate the ability of cells to survey the mechanical properties of their surrounding environment and suggest the possible involvement of both protein tyrosine phosphorylation and myosin-generated cortical forces in this process. Such response to physical parameters likely represents an important mechanism of cellular interaction with the surrounding environment within a complex organism.

3,013 citations