Signal transduction via integrin adhesion complexes

Abstract

Integrin adhesion complexes (IACs) have evolved over millions of years to integrate metazoan cells physically with their microenvironment. It is presumed that the simultaneous interaction of thousands of integrin receptors to binding sites in anisotropic extracellular matrix (ECM) networks enables cells to assemble a topological description of the chemical and mechanical properties of their surroundings. This information is then converted into intracellular signals that influence cell positioning, differentiation and growth, but may also influence other fundamental processes, such as protein synthesis and energy regulation. In this way, changes in the microenvironment can influence all aspects of cell phenotype. Current concepts envisage cell fate decisions being controlled by the integrated signalling output of myriad receptor clusters, but the mechanisms are not understood. Analyses of the adhesome, the complement of proteins attracted to the vicinity of IACs, are now providing insights into some of the primordial links connecting these processes. This article reviews recent advances in our understanding of the composition of IACs, the mechanisms used to transduce signals through these junctions, and the links between IACs and cell phenotype.

Differential functional roles of fibroblasts and pericytes in the formation of tissue-engineered microvascular networks in vitro

“…35,36 In addition, integrins are heterodimeric proteins critical for cell-matrix interactions, mechanotransduction, and cell signaling. 37 Consistent with our observation that ECFC and PCs form a common basement membrane, several ECM proteins were upregulated in PCs that are known to be part of vascular basement membranes 38 including collagen type IV isoforms, laminin chains, nidogen 1, SPARC, agrin, fibulin 2, and thrombospondin 1 and 2. In future studies, we will further investigate the critical factors that mediate the disparate interactions between ECFCs, FBs, and PCs.…”

Competence to epithelialise coincides with competence to differentiate in pluripotent cells

“…This raises the question of whether Tcf15's influence on adhesion and differentiation is regulated independently or whether adhesive changes might reinforce pro-differentiation signals. This is difficult to test because eliminating adhesion causes cell death in epiblast cells (Li et al, 2002;Migeotte et al, 2010), but it is tempting to speculate that differentiation competence may be enhanced by the ability of integrins to activate pro-differentiation signals (Humphries et al, 2018).…”

Adhesion force spectroscopy with nanostructured colloidal probes reveals nanotopography-dependent early mechanotransductive interactions at the cell membrane level

“…Mechanotransductive processes are involved in virtually all aspects of the cellular life and tissue organisation [11][12][13][14][15][16][17][18][19] and aberrations in components that participate to mechanosensing and mechanotransduction have been linked to various diseases, in particular in cancer and metastasis. A detailed comprehension of how biophysical ECM characteristics modulate mechanotransduction would promote new approaches for treatments of diseases, drug therapies or diagnostic approaches, exploiting and targeting identified mechanotransductive key regulators or structures 11,[20][21][22][23][24][25] .…”