Molecular complexity and dynamics of cell-matrix adhesions

Currently >50 proteins have been reported to be associated with focal conta cts and related ECM adhesions. Most of these contain multiple domains throu gh which they can interact with different molecular partners, potentially f orming a dense and heterogeneous protein network at the cytoplasmic faces o f the adhesion site. The molecular and structural diversity of this 'submem brane plaque' is regulated by a wide variety of mechanisms, including compe tition between different partner proteins for the same binding sites, inter actions triggered or suppressed by tyrosine phosphorylation, and conformati onal changes in component proteins, which can affect their reactivity. Inde ed, integrin-mediated adhesions can undergo dynamic changes in structure an d molecular properties from dotlike focal complexes to stress-fiber-associa ted focal contacts, which can further 'mature' to form fibronectin-bound fi brillar adhesions. These changes are driven by mechanical force generated b y the actin- and myosin-containing contractile machinery of the cells, or b y external forces applied to the cells, and regulated by matrix rigidity.