Mechanotransduction

Physical forces are central players in development and morphogenesis, provide an ever-present backdrop influencing physiological functions, and contribute to a variety of pathologies. Mechanotransduction encompasses the rich variety of ways in which cells and tissues convert cues from their physical environment into biochemical signals. These cues include tensile, compressive and shear stresses, and the stiffness or elastic modulus of the tissues in which cells reside. This article focuses on the proximal events that lead directly from a change in physical state to a change in cell-signaling state. A large body of evidence demonstrates a prominent role for the extracellular matrix, the intracellular cytoskeleton, and the cell matrix adhesions that link these networks in transduction of the mechanical environment. Recent work emphasizes the important role of physical unfolding or conformational changes in proteins induced by mechanical loading, with examples identified both within the focal adhesion complex at the cell-matrix interface and in extracellular matrix proteins themselves. Beyond these adhesion and matrix-based mechanisms, classical and new mechanisms of mechanotransduction reside in stretch-activated ion channels, the coupling of physical forces to interstitial autocrine and paracrine signaling, force-induced activation of extracellular proteins, and physical effects directly transmitted to the cell's nucleus. Rapid progress is leading to detailed delineation of molecular mechanisms by which the physical environment shapes cellular signaling events, opening up avenues for exploring how mechanotransduction pathways are integrated into physiological and pathophysiological cellular and tissue processes.