The molecular basis and specificity of integrin-ligand interactions.

Most eukaryotic cells have the ability to recognise and react functionally to adhesive extracellular matrices. This is true not only for actively migrating cells that use adhesive contact for traction and guidance, but also for stationary cells that require a platform for support and orientation. Cell-extracellular matrix adhesion has a homeostatic function in promoting tissue regeneration during wound healing, while aberrant adhesion contributes to the aetiology and pathogenesis of a number of major human diseases including arthritis, cardiovascular disease and cancer. Consistent with this multiplicity of function, extracellular matrices exhibit diversity in both composition and three-dimensional structure. The overall phenotypic effects induced by an extracellular matrix are the sum of multiple, specific ligand-receptor recognition events and therefore the relative distribution of receptors and ligands, in terms of both quantity and spatial presentation, needs to be considered. This structural complexity has however hampered progress towards an understanding of adhesive recognition events at the cellular level and, instead, a great deal of research effort has been concentrated on elucidating the mechanisms of adhesion at the molecular level. This has involved identifying both adhesion factors in extracellular matrices and the cell surface receptors recognising them, pinpointing the active sites in both sets of molecules that mediate ligand-receptor binding, and providing a three-dimensional description of the interactions. This commentary reviews the current state of this work.