UC Berkeley

Cells intricately sense mechanical forces from their surroundings, driving biophysical and biochemical activities. This phenomenon, known as mechanosensing, can occur at the cell-matrix interface. Here, mechanical forces resulting from cellular motion, such as migration or matrix stretching, are exchanged in part by the integrin receptor and its ligand, fibronectin. Upregulation of the integrin-fibronectin bond is associated with uncontrolled cell metastasis. Therefore, the molecular mechanisms of this bond are of interest to control cell behavior and limit cancer cell spreading. This bond operates through catch bond dynamics, wherein the bond lifetime paradoxically increases with greater force. However, the mechanism sustaining the characteristic catch bond dynamics of the integrin-fibronectin bond remains unclear. The work presented here leveraged multiscale biophysical simulations to uncover the molecular mechanisms underpinning integrin-fibronectin’s catch bond dynamics in the context of cell adhesion. This study integrated molecular dynamics simulations and finite element models to propose that fibronectin sites reinforce cell adhesion through enhanced binding properties and a mechanosensitive mechanism. This work sheds light on the mechanosensitive nature of cell-matrix interactions while contributing to our understanding of multiscale cellular behaviors in physiological and pathological environments.