The design of artificial extracellular matrices has attracted much attention in tissue engineering as well as in cell biology research. An immobilized recombinant epidermal growth factor (EGF), fused to an immunoglobulin G (IgG) Fc region (abbreviated as EGF-Fc) has been constructed. Mouse fibroblast Swiss 3T3 cells adhered both to EGF-Fc-coated and collagen-coated surfaces. Phosphorylation of EGF receptor in A431 cells was induced by immobilized EGF-Fc as well as soluble EGF. Immobilized EGF-Fc continuously activated mitogen-activated protein kinase (MAPK) in A431 cells whereas MAPK activation induced by soluble EGF decreased rapidly with time. The cytoskeleton of A431 cells adhering onto immobilized EGF-Fc was filopodia whereas that of the cells adhering onto collagen in the presence of soluble EGF was lammellipodia.