Multistable mechanosensitive behavior of cell adhesion driven by actomyosin contractility and elastic properties of force-transmitting linkages.

Abstract

The ability of cells to sense the mechanical properties of their microenvironment is essential to many physiological processes. The molecular clutch theory has played an important role in explaining many mechanosensitive cell behaviors. However, its current implementations have limited ability to understand how molecular heterogeneity, such as adhesion molecules with different elasticities, regulates the mechanical response of cell adhesion. In this study, we developed a model incorporating the experimentally measured elastic properties of such proteins to investigate their influence on cell adhesion. It was found that the model not only could accurately fit previous experimental measurements of cell traction force and retrograde actin flow, but also predicted multistablility of cell adhesion as well as a feedback loop between the densities of the extracellular matrix proteins and contractile myosin II motors in living cells. The existence of such a feedback loop was successfully confirmed in experiments. Taken together, our study provides a theoretical framework for understanding how the mechanical properties of adaptor proteins, local substrate deformations and myosin II contractility affect cell adhesion across different cell types and physiological conditions.