Modeling the Mechanosensitivity of Crawling Cells

In this work, we study the ability of cells to probe and dynamically adapt to the mechanical properties of their surroundings, i.e., their mechanosensitivity. Experimentally, this can be studied by observing the reorientation of crawling cells over cyclically stretched substrates. To understand the observed cell-specific reorientation, we have introduced a computational model that couples the cyclically stretched substrate to the sub-cellular elements responsible for cell shape and motility: cell membrane, actin cytoskeleton, and focal adhesions. Depending on which sub-cellular process is being probed, and the type of coupling with the substrate, our simulations predict either no reorientation, a bi-stability in the parallel and perpendicular directions, or a complete reorientation. In particular, we show that an asymmetry in the adhesion dynamics during the loading and unloading phases of the stretching can be used to selectively align the cells. Our results provide further evidence for the importance of focal adhesion dynamics in determining the mechanosensitive response of cells.