Modeling the mechanosensitivity of fast-crawling cells on cyclically stretched substrates.

The mechanosensitivity of cells, which determines how they are able to respond to mechanical signals, is crucial for the functioning of biological systems. Experimentally, this is investigated by studying the reorientation of cells on cyclically stretched substrates. The reorientation depends on the type of cell and on the stretching protocol, but the mechanisms responsible for the response are still not completely understood. Here, we introduce a computational model for fast crawling cells on cyclically stretched substrates that accounts for the sub-cellular elements responsible for cell shape and motility. This includes the dynamics of the cell membrane, the actin cytoskeleton, and the focal adhesions with the stretching substrate. These processes evolve over characteristic time scales that can vary by orders of magnitude and naturally give rise to the frequency dependent reorientation observed experimentally. Depending on which processes are being probed by the stretching and on 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 either the parallel or perpendicular direction. In particular, we show that an asymmetry in the adhesion dynamics during the loading and unloading phases of the stretching, whether it comes from the response of the cell itself or from the precise stretching protocol, 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, as well as a way to interpret recent experiments.