Environmental sensing through focal adhesions

Abstract

The aim of this Review is to discuss how molecular research into the complex interplay between cell adhesion and the cytoskeleton, combined with advanced surface nanoengineering technologies, can shed light on the mechanisms by which cells sense the neighbouring microenvironment and nanoenvironment. Cells demonstrate an extraordinary capacity to respond to a wide range of features of the surrounding matrix, including its chemical nature and physical properties. Contemporary methods of microfabrication and nanofabrication enable the production of substrates with well-defined topography, rigidity, ligand spacing and anisotropy. Plating cells on surfaces with diverse physical properties has revealed the exquisite capacity of cells to sense, and differentially respond, to such adhesive matrices. Mechanical modulation of the various adhesion complexes leads to the generation of integrin-mediated signals that affect multiple features of cell shape, activity and fate. The mechanosensitivity of integrin-based adhesions (focal adhesions) is attributable to the complexity and modularity of the adhesion complexes, and their different functional modules. Specifically, mechanosensitive elements can be found in essentially every structural–functional module of the adhesion sites, including the extracellular matrix itself, the integrin receptors, the actin-linking and actin polymerization machinery, and the signal-generating and transducing modules. Owing to the overall, combined mechanosensitivity of focal adhesions, cytoskeleton-generated forces affect the initiation, maturation and further growth of these structures. In turn, the pre-existing integrin adhesions determine the organization of the actin cytoskeleton by creating boundary conditions that determine the spatial organization of the cytoskeleton; by inducing actin polymerization at the local level; and by global signalling, mainly through the Rho pathways, thereby regulating the overall assembly of the actin-containing structures. Focal adhesions seem to be responsible for the spatio-temporal coordination of the multiple signalling events that are triggered by cell–extracellular matrix interactions.