On the mechanism of durotaxis in motile cells
Sylvain Gabriele (University of Mons)
Mechanics and Physics of Biological Cells
Wed 9:00 - 10:30
Barus-Holley 141
Shape, speed and directionality of crawling cells are determined by many dynamic processes of the cytoskeleton and also cell-substrate interactions. Many studies have characterized the morphological and mechanical modifications of stationary cells in response to the substrate stiffness; yet, there have been no comprehensive efforts to elucidate the mechanism by which matrix rigidity determines motile cell behavior. To address this issue, we studied fish keratocytes, which are among the fastest moving animal cells and are able to maintain nearly constant speed and direction during movement. The molecular dynamism of these cells, combined with the persistence of their global shape and behaviour, make them an ideal model system for investigating the mechanisms of durotaxis in motile cells. We examined the morphology, the directionality and the organization of adhesions, myosin II, and the actin network in keratocytes migrating on homogeneous substrates over a wide range of stiffnesses. On the basis of quantitative observations of a large number of cells, we demonstrate a close relationship between morphological and migrating parameters, suggesting that the substrate stiffness dictates the level of polarization and directionality of motile cells. Remarkably, motile cells were observed to maintain a constant spreading area during their polarization over seven orders of magnitude in rigidities, in contrary to previous reports on stationary cells. We further demonstrate that the physical linkage between the cytoskeleton and the substrate is significantly affected by the matrix stiffness and is required for cell polarization. On the whole, our results are consistent with a quantitative physical model in which the overall keratocyte behavior (shape, polarization and directionality) emerges from the impact of the matrix stiffness on the formation of focal adhesions that creates a frictional slippage, which, in turn, balances myosin-mediated contractile forces.