The role of the surface membrane in regulating proliferation and differentiation of eukaryotic cells is highly complex. Proximal cell-cell interactions are involved, including physical contact via junctional complexes, exfoliation of surface membrane vesicles, proteolytic cleavage of membrane-bound precursors, and exocytosis of soluble proteins (see Fig 5). At another level, the surface expresses receptors and other proteins that mediate cell-cell adhesion, a multistep event that may be sufficient to activate some growth-associated genes and alter cell shape. The evidence indicates that together with secreted growth factors, surface membrane-associated molecules play a dynamic role in regulating multicellular assembly and cell differentiation and growth.