Contact Stiffness Governs Mechanoresponses of Living Cells to Extracellular Microenvironment

Extracellular microenvironment properties (including physical, chemical and geometrical aspects) have profound effects on the fate of living cells. However, the interplay underlying these regulations remains unclear. Based on the fact that interaction of living cells with extracellular matrix (ECM) is a typical contact problem, we proposed a contact stiffness (CS)-based model to address cell mechanoresponses. Our model provides a unified means to address the effect of physical parameters e.g. intrinsic ECM stiffness and geometrical factors including ECM thickness and cell spreading area on cell behaviors, such as stem cell differentiation and YAP activation in different experimental conditions. We show that the CS for living cells contact with ECM is not merely a passive variable but can be actively tuned by cell itself, and thus help understand the response of cells to non-adjacent layer of layered ECM. We also reveal that the broad variation range of CS is an intrinsic characteristic of a certain cell type which reflects its “mechanical plasticity” in response to extracellular microenvironment. ### Competing Interest Statement The authors have declared no competing interest.