Nucleation and decay initiation are the stiffness-sensitive phases of focal adhesion maturation

Abstract

A cell plated on a two-dimensional substrate forms adhesions with that surface. These adhesions, which consist of aggregates of various proteins, are thought to be important in mechanosensation, the process by which the cell senses and responds to the mechanical properties of the substrate (e.g., stiffness). On the basis of experimental measurements, we model these proteins as idealized molecules that can bind to the substrate in a strain-dependent manner and can undergo a force-dependent state transition. The model forms molecular aggregates that are similar to adhesions. Substrate stiffness affects whether a simulated adhesion is initially formed and how long it grows, but not how that adhesion grows or shrinks. Our own experimental tests support these predictions, suggesting that the mechanosensitivity of adhesions is an emergent property of a simple molecular-mechanical system.