Integrins in mechanotransduction

Abstract

Forces acting on cells govern many important regulatory events during development, normal physiology, and disease processes. Integrin-mediated adhesions, which transmit forces between the extracellular matrix and the actin cytoskeleton, play a central role in transducing effects of forces to regulate cell functions. Recent work has led to major insights into the molecular mechanisms by which these adhesions respond to forces to control cellular signaling pathways. We briefly summarize effects of forces on organs, tissues, and cells; and then discuss recent advances toward understanding molecular mechanisms.

Figure 1. Partial summary of responses of integrin-mediated adhesions to force

Cells adhered to extracellular matrix (blue fabric) under (A) lower force or (B) high force. Force stimulates conversion of integrins from low affinity states (red) to more stable, high affinity states (green); stretching of talin (light green) to recruit vinculin (orange); also, additional integrins are activated and recruited to the adhesions. YAP (and TAZ) translocate to the nucleus to induce expression of cell cycle and differentiation genes. Zyxin localizes to focal adhesions under moderate force and at higher forces to actin stress fibers and the nucleus, where it promotes repair of the stress fibers and new gene expression.

Figure 2. Molecular tension sensors

These methods all use a FRET pair, denoted here as blue and yellow fluorescent proteins, connected by an elastic element, denoted by a spring. Tension extends the spring, which decreased FRET efficiency.