Focal adhesions, stress fibers and mechanical tension

Abstract

Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discuss the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function.

Keywords: Integrins; Myosin II; RhoA; Substratum rigidity.

Fig. 1

Types of stress fiber in migrating cells. Schematic representation of SFs in motile cells, (a) top and (b) side views. Four categories of SFs are observed: dorsal SFs, transverse arcs, ventral SFs and the perinuclear actin cap.

Fig. 2

Mechanical tension activates signaling pathways at adhesion sites. a. Exposure of cryptic sites. Tension can affect protein conformation to expose protein binding sites (e.g. talin) or sites for kinases or other protein modifications (e.g. p130cas). b. RhoA regulation of adhesion maturation through Rock and mDia. Adhesion to fibronectin activates RhoA through p115 RhoGEF and LARG [91], leading to Rock-mediated myosin stimulation. In response to tension, GEF-H1, LARG and mDia are recruited [32,37] and promote actin polymerization. B1 (1) and αv (2) integrin subtypes cooperate to regulate RhoA signaling and adhesion maturation [62].