Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The goal of this study was to determine the morphological and sub-cellular mechanical effects of Rac activation on fibroblasts within 3-D collagen matrices. Corneal fibroblasts were plated at low density inside 100 microm thick fibrillar collagen matrices and cultured for 1-2 days in serum-free media. Time-lapse imaging was then performed using Nomarski DIC. After an acclimation period, perfusion was switched to media containing PDGF. In some experiments, Y-27632 or blebbistatin were used to inhibit Rho-kinase (ROCK) or myosin II, respectively. PDGF activated Rac and induced cell spreading, which resulted in an increase in cell length, cell area, and the number of pseudopodial processes. Tractional forces were generated by extending pseudopodia, as indicated by centripetal displacement and realignment of collagen fibrils. Interestingly, the pattern of pseudopodial extension and local collagen fibril realignment was highly dependent upon the initial orientation of fibrils at the leading edge. Following ROCK or myosin II inhibition, significant ECM relaxation was observed, but small displacements of collagen fibrils continued to be detected at the tips of pseudopodia. Taken together, the data suggests that during Rac-induced cell spreading within 3-D matrices, there is a shift in the distribution of forces from the center to the periphery of corneal fibroblasts. ROCK mediates the generation of large myosin II-based tractional forces during cell spreading within 3-D collagen matrices, however residual forces can be generated at the tips of extending pseudopodia that are both ROCK and myosin II-independent.
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PMID:Dynamic assessment of fibroblast mechanical activity during Rac-induced cell spreading in 3-D culture. 1845 53

The goal of this study was to investigate the responses of isolated cells in 3-D culture to localized application of mechanical and biochemical signals. Corneal fibroblasts were plated inside collagen matrices for 24 hours, then imaged using time-lapse DIC. For mechanical perturbation, a microinjection needle (Femtotip) was inserted axially into the ECM, then displaced laterally to alter local ECM stress. For biochemical stimulation, PDGF or vehicle control solution was microinjected into the matrix. Compressing the ECM perpendicular to the cell axis had no appreciable effect on cell behavior. However, pushing the ECM parallel to the cell axis induced rapid cellular contraction, followed by secondary cell spreading and tractional force generation. Injection of PDGF induced a similar cell spreading response. Cells in 3-D matrices showed remarkable plasticity, and extension of pseudopodia could be induced at both the leading and trailing edges of migrating cells.
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PMID:Localized application of mechanical and biochemical stimuli in 3-D culture. 1869 23