SPATIALLY CONTROLLED ADHESION, SPREADING, AND DIFFERENTIATION OF ENDOTHELIAL-CELLS ON SELF-ASSEMBLED MOLECULAR MONOLAYERS

Chemically modified glass substrates were used to demonstrate differen tial adhesion, growth, and differentiation of endothelial cells. Endot helial cells were examined for adhesion and growth on glass, glass tre ated with N-(2-aminoethyl)-3-aminopropyl trimethoxysilane (EDA), or ED A with a subsequent treatment with physically adsorbed extracellular m atrix components human fibronectin and heparin sulfate. EDA and EDA/hu man fibronectin showed similar abilities to support adhesion, spreadin g, and proliferation of endothelial cells. In contrast, heparin sulfat e inhibited endothelial cell adhesion to EDA. Differentiation of endot helial cells resulting in precapillary cord formation was triggered by addition of basic fibroblast growth factor (bFGF), On EDA and EDA/hum an fibronectin bFGF causes confluent endothelial cell monolayers to di fferentiate and form cords, which resulted in a large-scale spatial re distribution of cells on the surface. Formation of organized neovascul ar assemblies was demonst ated on coplanar molecular patterns of EDA a nd a nonadhesive perfluorinated alkylsilane ro-1,1,2,2-tetrahydrooctyl )-1-dimethylchlorosilane (13F). Endothelial cells preferentially adher ed to the EDA lines and after 24-48 hr, microfilaments aligned with th e long axes of the patterned EDA region. Finally, endothelial cells th at became confluent within the confines of the EDA region (bound by th e nonadhesive, 13F domains) were observed to differentiate into neovas cular cords in long-term culture (7-10 days) with bFGF.