The Matrix Stiffness Regulates Morphology, Direction and Persistence of Motiles Cells

Abstract

Cell motility is a fundamental process for embryonic development, wound healing, immune responses and for pathological processes such as cancer metastasis. During past few decades, the influence of the extracellular matrix stiffness, known as durotaxis, has been extensively studied on stationary cells. However, the impact of the matrix stiffness on the motion of motile cells is still unclear. By using a wide range of ECM stiffnesses with a contant cell-ligand density, we have investigated morphological and dynamical parameters of fish keratocytes in response to a wide range of matrix stiffnesses. We have found that modifying the matrix rigidity of the underlying substrate has a dramatic effect on keratocyte motility and directional persistence. To elucidate the mechanisms by which the matrix stiffness determines moving cell behavior, we examined the organization of adhesions, myosin II, and the actin network in keratocytes migrating on substrates with a wide range of stiffnesses and a constant surface chemistry. Our results are consistent with a quantitative physical model in which keratocyte shape and migratory behavior emerge from the self-organization of actin, cell-substrate adhesions and myosin II activity.