Lamellipodia (LP), a subcellular structure at cell front, plays a key role in cell spreading and migration. And its mechanosensing function is of crucial importance for cell activities. But the mechanism of the mechanosensing function remains poorly understood. Here we developed a multiscale model to consider its protrusion and retraction processes, and analyzed the forces acted on the key structural components of the LP and the effect of these forces on LP movement. Our results show that raising substrate rigidity increases the force acting on the focal adhesion (FA) and decreases the force on LP actin, thus promoting the maturation of FA while suppressing the detachment of LP actin from the cell membrane. The membrane tension also influences the LP movement, but its effect is opposite to that of the substrate rigidity. It turns out that the substrate rigidity and membrane tension together regulate the dynamics of FAs and the detachment of LP actin, which in turn determine the LP movement. Interestingly, we found that the effect of substrate rigidity and membrane tension on the LP movement both exhibit a biphasic manner. We show that our predictions agree, in general, with the experiments on cell mechanosensing behaviors at both subcellular and cellular levels.
Keywords: cell membrane; cell migration; cell spreading; focal adhesion; lamellipodium.