Elasticity of adhesion bonds determines multistable mechanosensitive behaviour of living cells

Abstract

The ability of cells to sense the mechanical properties of their microenvironment is essential to many physiological processes. Previously, the molecular clutch theory was developed to explain many mechanosensitive cell behaviours. However, because it does not take into account the nonlinear elastic properties of key proteins involved in the formation of cell adhesion complexes, this theory cannot establish a relationship between mechanosensitive cell adhesion behaviour and the force response of underlying proteins observed in single-molecule experiments. In this study, we developed a model incorporating the experimentally measured nonlinear elastic properties of such proteins to investigate their influence on cell adhesion behaviour. It was found that the model not only could accurately fit previous experimental measurements of the cell traction force and the retrograde actin flow, but also predicted multistable cell adhesion behaviour along with a feedback loop between the densities of the extracellular matrix proteins and myosin II motors in living cells. Existence of the latter was successfully confirmed in experiments on NIH-3T3 cells. Taken together, our study provides a theoretical framework for understanding how the mechanical properties of adapter proteins, local substrate deformations and myosin II contractility affect cell adhesion behaviour across different cell types and physiological conditions.