Stressing the limits of focal adhesion mechanosensitivity

Abstract

Focal adhesion assembly and maturation often occurs concomitantly with changes in force generated within the cytoskeleton or extracellular matrix. To coordinate focal adhesion dynamics with force, it has been suggested that focal adhesion dynamics are mechanosensitive. This review discusses current understanding of the regulation of focal adhesion assembly and force transmission, and the limits to which we can consider focal adhesion plaques as mechanosensitive entities.

Figure 1

Schematic of the stages of adhesion assembly from (left) nascent adhesion formation within the lamellipodium (middle) adhesion stabilization at the lamellipodium/lamella interface and (right) adhesion maturation associated with stress fiber assembly at the adhesion plaque. Focal adhesion growth rate is identical to stress fiber growth rate and both are correlated to actin retrograde flow. Above a critical tension threshold of ~1 nN, adhesion growth rate is independent of changes to intracellular tension.

Figure 2

Schematic of force transmission by focal adhesion plaques both during nascent adhesion assembly (left) and after engagement to the ECM and production of traction force (middle). The complex macromolecular interactions can be modeled as a dynamic friction with labile bonds between multiple interfaces (right). The effective friction coefficients change as a function of force applied to the focal adhesion, with the strength of the integrin–ECM interface increasing dramatically compared to the strength of the actin-focal adhesion interface during adhesion engagement.