Cell adhesion as dynamic interplay of lock-and-key, generic and elastic forces

The selectivity of cell-cell and cell-tissue adhesion is determined by specific short range forces between cell surface proteins. Long range entropic interfacial forces (mediated by repeller molecules and membrane undulations) and adhesion-induced elastic stresses in the cell envelope serve the fine control of the strength and duration of adhesion. The initial step of cell adhesion exhibits typical features of a first order wetting transition resulting in the formation of tight adhesion domains by lateral phase separation of receptors. External lift forces can cause shrinking and unbinding of adhesion sites if the receptors are immobile but induce domain growth if they are mobile. Strong adhesion domains (resisting nano-Newton forces) can form by commitment of some 10,000 receptors enabling cells to control adhesion strength rapidly by varying the receptor and repeller densities on cell surfaces through endocytosis and exocytosis. The adhesion domains can function as constraint reaction spaces facilitating the local assembly of actin stress fibers and control cell signalling processes as shown for the activation of immunological responses by immunological synapses.