Molecular and biological interactions of fibronectin.

Abstract

Fibronectin is a high molecular weight glycoprotein present at cell surfaces and in various body fluids. It is involved in cellular adhesion. The frequent absence of fibronectin from the surface of malignant cells may contribute to the invasive growth of tumors. To develop a better understanding of the functions of fibronectin, we have studied its structure by making use of proteolytic fragmentation and monoclonal antibodies. Fragments of plasma fibronectin which retain one or several of the affinities of intact fibronectin have been purified using affinity chromatography on collagen and heparin, and on monoclonal antibodies. These studies reveal a structure in which the different functions are located in separate protease-resistant molecular domains. The NH2-terminal domain contains the binding sites for fibrin, actin, and Staphylococci; this is followed by a collagen-binding domain, the cell attachment domain, and at the COOH-terminal end, the heparin-binding domain. These binding sites allow fibronectin to participate in multiple interactions with collagens and proteoglycans. The insoluble complexes formed by these 3 components that can be generated in vitro may represent a model for the basic structure of extracellular matrices. The role of fibronectin in such a matrix may be to contribute to the stability of the complex and to provide adhesion sites for cells. Disturbances in the interactions involving fibronectin could be potentially important to understanding diseases of connective tissues and in malignancy.