Alireza S. Sarvestani
Recent in vitro studies have highlighted the importance of substrate stiffness in governing a range of cellular functions. Motility of adherent cells, in particular, is found to be regulated by the substrate rigidity. Many cell types exhibit a subtle biphasic migration-velocity response to increasing substrate rigidity, with fast migration occurring at intermediate stiffness and slower migration on very compliant or highly rigid substrates. This study aims at improving the understanding of mechanisms responsible for cell sensitivity to the mechanical stiffness of extracellular environment during migration. We use the "two-spring model" as a mechanistic paradigm for rigidity sensing ability of cells at the scale of a single adhesion site. This will be implemented in a simple physical model of cell motility to elucidate how the local autonomy at the scale of adhesion sites may spatially and temporally regulate the cell motility. The model predicts a bell-shaped dependence between the speed of locomotion and substrate rigidity, similar to the experimental observations. This behavior is demonstrated to be rooted in the different effect of substrate rigidity on the magnitude of anterior and posterior actomyosin contractile forces which leads to the variation of net traction in a biphasic fashion.
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