Theory of force regulation by nascent adhesion sites

Abstract

The mechanical coupling of a cell with the extracellular matrix relies on adhesion sites, clusters of membrane-associated proteins that communicate forces generated along the F-Actin filaments of the cytoskeleton to connecting tissue. Nascent adhesion sites have been shown to regulate these forces in response to tissue rigidity. Force-regulation by substrate rigidity of adhesion sites with fixed area is not possible for stationary adhesion sites, according to elasticity theory. A simple model is presented to describe force regulation by dynamical adhesion sites.

FIGURE 1

Initial adhesion site. Dimeric integrin transmembrane proteins bind to specific substrate ligands, such as fibronectin, as well as to the Talin I adaptor proteins of the cytoplasm. Talin I, in turn, is linked to the actin filaments of the cytoskeleton along which traction forces are generated. Reinforcement of the adhesion site involves recruitment of Vinculin proteins (figure adapted from Ref. 4).

FIGURE 2

Dependence of the adhesion-site dissociation force on substrate stiffness obtained from Eq. 10. Vertical axis is the most likely dissociation force divided by the thermal force scale f_β = k_BT/ρ_f, with ρ_f the characteristic scale of the potential linking the adhesion site to the actin filament bundle. Horizontal axis is the substrate stiffness k ≈ Ya, with Y the Young's Modulus, and a the adhesion-site dimension divided by the stiffness scale with J the zero-force escape rate of the adhesion site in the slip state and with V_R the retrograde velocity. The lower branch corresponds to a slipping adhesion site, terminating at a critical stiffness. The upper branch corresponds to a reinforced state that fully transmits traction to the substrate. Once the system is reinforced, it will not return to the slip state.