Interplay Between Mechanosensitive Adhesions and Membrane Tension Regulates Cell Motility

Abstract

The initiation of directional cell motion requires symmetry breaking that can happen with or without external stimuli. During cell crawling, forces generated by the cytoskeleton and their transmission through mechanosen-sitive adhesions to the extracellular substrate play a crucial role. In a recently proposed one-dimensional model [P. Sens, Proc. Natl. Acad. Sci. USA 117 , 24670 (2020)], a mechanical feedback loop between force-sensitive adhesions and cell tension was shown to be sufficient to explain spontaneous symmetry breaking and multiple motility patterns through stick-slip dynamics, without the need to account for signaling networks or active polar gels. We extend this model to two dimensions to study the interplay between cell shape and mechanics during crawling. Through a local force balance along a deformable boundary, we show that the membrane tension coupled with shape change can regulate the spatiotemporal evolution of the stochastic binding of mechanosensitive adhesions. Linear stability analysis identifies the unstable parameter regimes where spontaneous symmetry breaking can take place. Using simulations to solve the fully coupled nonlinear system of equations, we show that, starting from a randomly perturbed circular shape, this instability can lead to keratocyte-like shapes. Simulations predict that different adhesion kinetics and membrane tension can result in different cell motility modes including gliding, zigzag, rotating, and sometimes chaotic movements. Thus, using a minimal model of cell motility, we identify that the interplay between adhesions and tension can select emergent motility modes. DOI: 10.1103/PRXLife.1.023007