We will carry out a coordinated cell biological and biochemical analysis of protein-protein interactions at the cell surface and their role in several related cellular functions. Our particular focus will be on the glycoprotein fibronectin, and its interactions with other proteins both outside the cell and across the membrane with actin microfilaments. Fibornectin is involved in adhesion, spreading and migration of fibroblasts and is reduced in amount by oncogenic transformation. Fibronectin has also been implicated in the interaction of platelets with collagen and as an opsonin in phagocytosis. We will investigate the involvement of fibronectin in these phenomena by functional assays, immunofluorescence, and electron microscopy, and will study its interactions with other proteins by chemical crosslinking reagents and affinity chromatography. This study will provide information about multimolecular interactions at the cell surface and transmembrane connections with the cytoskeleton and their involvement in several important cellular and physiological properties (oncogenic transformation, adhesion, migration, hemostasis, phagocytosis).