Mechanotransduction via Integrins

Abstract

During life and development, tissues and individual cells within an organism are under several types of mechanical stress. Forces are being exerted upon cell-matrix adhesions both from the extracellular environment and from within the cell, as the cytoskeleton actively generates tension. These mechanical cues are efficiently transduced via integrins, receptors for extracellular matrix components which are found in adhesive sites and are connected to the actin cytoskeleton. Through modulating the strength of these focal complexes and focal adhesions, as well as remodelling the cytoskeleton, forces from within the cell are balanced by those encountered on the outside, thereby balancing the tensional state of the cell. It appears that increased forces upon integrins correlate with greater intracellular tension via actomyosin contractility, as well as greater cell spreading. This occurs via the actions of small GTPases which balance actin polymerization and contractility, leading to adhesion modulation, while microtubules act as compressional struts to balance the generated tension. In addition to tensional and adhesive remodelling in response to applied forces, mechanotransduction via integrins also influences cell fate. In this work we look at the evidence that integrins efficiently transduce mechanical stresses and aid in the tensionally balanced state of the cell. Furthermore, we outline some general signalling mechanisms via which forces upon integrins affect processes as widespread as migration, proliferation, differentiation and apoptosis. It appears that downstream signal transduction impinges on most general growth and survival pathways, and that adhesion-mediated signalling is essential for a physiological tissue state. This therefore emphasizes the importance of mechanical tension sensing via cell-matrix adhesions in all cells, and perturbations in either integrins or their associated signalling and cytoskeletal machinery, as well as disturbed extracellular forces, can lead to pathological situations and malignancy.