Adhesion-induced receptor segregation and adhesion plaque formation: A model membrane study

A model system to study the control of cell adhesion by receptor-mediated s pecific forces, universal interactions, and membrane elasticity is establis hed. The plasma membrane is mimicked by reconstitution of hemophilic recept or proteins into solid supported membranes and, together with lipopolymers, into giant vesicles with the polymers forming an artificial glycocalix. Th e homophilic cell adhesion molecule contact site A, a lipid-anchored glycop rotein from cells of the slime mold Dictyostelium discoideum, is used as re ceptor. The success of the reconstitution, the structure and the dynamics o f the model membranes are studied by various techniques including film bala nce techniques, micro fluorescence, fluorescence recovery after photobleach ing, electron microscopy, and phase contrast microscopy. The interaction of the functionalized giant vesicles with the supported bilayer is studied by reflection interference contrast microscopy, and the adhesion strength is evaluated quantitatively by a recently developed technique. At low receptor concentrations adhesion-induced receptor segregation in the membranes lead s to decomposition of the contact zone between membranes into domains of st rong (receptor-mediated) adhesion and regions of weak adhesion while contin uous zones of strong adhesion form at high receptor densities. The adhesion strengths (measured in terms of the spreading pressure S) of the various s tates of adhesion are obtained locally by analysis of the vesicle contour n ear the contact line in terms of elastic boundary conditions of adhesion: t he balance of tensions and moments. The spreading pressure of the weak adhe sion zones is S approximate to 10(-9) J/m(2) and is determined by the inter play of gravitation and undulation forces whereas the spreading pressure of the tight adhesion domains is of the order S approximate to 10(-6) J/m(2).