Integrins and Extracellular Matrix in Mechanotransduction

Abstract

Integrins bind extracellular matrix fibrils and associate with intracellular actin filaments through a variety of cytoskeletal linker proteins to mechanically connect intracellular and extracellular structures. Each component of the linkage from the cytoskeleton through the integrin-mediated adhesions to the extracellular matrix therefore transmits forces that may derive from both intracellular, myosin-generated contractile forces and forces from outside the cell. These forces activate a wide range of signaling pathways and genetic programs to control cell survival, fate, and behavior. Additionally, cells sense the physical properties of their surrounding environment through forces exerted on integrin-mediated adhesions. This article first summarizes current knowledge about regulation of cell function by mechanical forces acting through integrin-mediated adhesions and then discusses models for mechanotransduction and sensing of environmental forces.

E-cadherin is under constitutive actomyosin-generated tension that is increased at cell–cell contacts upon externally applied stretch

“…Cell adhesion proteins are structural and functional hubs between the cytoskeleton and the extracellular environment and hence are strategically positioned to transduce mechanical signals (45). Mechanotransduction through integrin adhesion proteins to the extracellular matrix is well studied (46). Protein components in these adhesion complexes respond directly to mechanical forces by changing conformation, which exposes cryptic binding sites to putative binding partners and phosphorylation (47,48).…”

Amino Acid Transport Associated to Cluster of Differentiation 98 Heavy Chain (CD98hc) Is at the Cross-road of Oxidative Stress and Amino Acid Availability

“…We show that expression of the CD98hc portion able to bind integrins (C98T98E69) in CD98hc-null cells is not sufficient to restore in vitro cell proliferation, in contrast with in vivo teratoma formation (6), suggesting a specific integrin mediated regulation depending on the properties of the surrounding environment (43). In parallel, expression of any of the chimeras deficient for integrin interaction but containing the CD98hc-ED (C69T98E98, C98T69E98) (6, 10) rescues in vivo and in vitro cell proliferation of CD98hc-deficient cells.…”

Cell-material interaction

“…Transduction of forces by cells is bidirectional, cells exert forces and are able to sense mechanical forces applied to cells. Integrins are regarded as mechanotransducers that facilitate the mechanical coupling between outside the cell and the cytoskeleton [38]. The mechanical interaction of integrins with the cytoskeleton involves accumulation of a number of cytoskeletally associated proteins [39,40].…”