The classical approach to understanding the closeness of approach of two membranes has developed from consideration of the net effect of an attractive van der Waals force and a repulsive electrostatic force. The repulsive role of hydration forces and stereorepulsion glycocalyx forces have been recently recognized and an analysis of the effect of crosslinking molecules has been developed. Implicit in these approaches is the idea of an intercellular water layer of uniform thickness which narrows but retains a uniform thickness as the cells move towards an equilibrium separation distance. Most recently an attempt has been made to develop a physical chemical approach to contact which accommodates the widespread occurrence of localized spatially separated point contacts between interacting cells and membranes. It is based on ideas drawn from analysis of the conditions required to destabilize thin liquid films so that thickness fluctuations develop spontaneously and grow as interfacial instabilities to give spatially periodic contact. Examples of plasma membrane behaviour which are consistent with the interfacial instability approach are discussed and experiments involving polycation, polyethylene glycol, dextran and lectin adhesion and agglutination of erythrocytes are reviewed.

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