How do cells sense and respond to adhesive contacts? Diffusion-trapping of laterally mobile membrane proteins at maturing adhesions may initiate signals leading to local cytoskeletal assembly response and lamella formation.

A great deal is known about the ways in which diffusible molecules bind to receptors and trigger transductive mechanisms located in the plasma membrane. Only recently has there been a wider appreciation of the fact that contacts between cells and surfaces on which they can spread may also initiate cytoplasmic signals. This embraces cell-to-cell contact as well as adhesion to noncellular surfaces. In the former category, signal transduction through the T-cell receptor complex (Littman, 1989) can activate adhesion based on LFA-l/lCAM-1 by a servo-motor effect (Dustin and Springer, 1989; van Seventer et al. 1990; review, Springer, 1990). Very recently, Lo et al. (1991) have demonstrated that adhesion of neutrophils to endothelium by means of E selectin (ELAM-1) generates signals responsible for increased adhesion by the LFA-l/lCAM-1 mechanism. One of the first clearly defined examples of a signal initiated by the adhesion of cells to a substratum was provided by the important experiment of Wright et al. (1983). They showed that when macrophages spread on a surface bearing fibronectin, engagement of a # integrin resulted in a signal that spread to the upper membrane where it enabled the two distinctly different complement receptors CR-1 (immunoglobulin superfamily) and CR-3 (one of the leucocyte integrins, now called Mac-1 or CDllb/CD18) to internalize particles bearing the corresponding ligands C3b or iC3b. No change in the number of surface receptors is involved. The effect was reversed on re-spreading the cells on a surface lacking fibronectin. Similar results with a laminin-coated surface were reported by Bohnsack et al. (1985). Blood platelet activation by contact with the substratum also involves signalling (reviews by Parise, 1989; Andrews and Fox, 1990). Almost any surface except vascular endothelium and certain polymers (Gingell et al. unpublished) can activate platelets. The response includes rapid spreading, exocytosis and cytoskeletal reorganization associated with changes in the levels of second messengers and the activation of protein kinases, apparently regulated by glycoprotein lib, Ilia (Ferrell and Martin, 1989; Golden et al. 1990). Localized signalling processes have also been implicated in the recognition of extracellular matrix molecules and other surfaces by fibroblasts (reviewed by Zetter and Brightman, 1990). This involves integrinmediated adhesion and the assembly of linkages between membrane receptors and the cytoskeleton, resulting in the formation of focal contacts. Massia and Hubbell (1991) have recently studied the relationship between the density of RGD peptides bound to a substratum and the clustering of integrin receptors, leading to focal contact formation. Curtis (1987) has argued that adhesion, particularly to fibronectin, may trigger cell activation, and an innovative study by Curtis et al. (1992) has strongly implicated integrin-mediated signalling in the activation of a non-integrin-based adhesion mechanism in cultured BHK cells.