Transmembrane crosstalk between the extracellular matrix and the cytoskeleton

Cell adhesions represent the interaction interfaces between cells and the extracellular matrix. Their study provides exciting insights into the interplay between physical forces and molecular signalling in cell regulation. Cells use transmembrane actin–integrin adhesion complexes as mechanosensors to probe the rigidity of the extracellular environment, mediate adhesion, trigger signalling, and remodel the extracellular matrix (ECM). Local physical forces induce transitions in the types and functions of these cell–matrix adhesions: Focal complexes transform into focal adhesions, which serve as the source of fibrillar adhesions. Integrin translocation appears to stretch fibronectin molecules, exposing cryptic sites that mediate matrix assembly into extracellular fibrils. A key mechanism in these transitions appears to be conformational changes induced by force or a local reorganization of scaffold or signalling molecules to promote multimolecular assembly. Both intracellular molecular-complex formation at adhesion sites and ECM assembly are regulated by Rho-family GTPases. The main challenges for the future include:  The identification of the full repertoire of adhesion-associated molecules.  Comparison of the various 'focal complex'-like structures.  Characterization of the molecular and cellular nature of the mechanosensors involved in cell–matrix adhesion.  Characterization of the regulation and functional integration of the various forms of adhesions, which change depending on the state of differentiation, tissue location, and application of local forces.  Exploring the structure and function of cell–matrix adhesions in three-dimensional microenvironments in vivo and explaining the roles of complex carbohydrates in cell–matrix interactions.