ENDOTHELIAL-CELL INTERACTIONS WITH SYNTHETIC PEPTIDES FROM THE CARBOXYL-TERMINAL HEPARIN-BINDING DOMAINS OF FIBRONECTIN

Fibronectin (FN) plays an important role in endothelial cell adhesion, spreading, and motility. Within FN, a number of functional domains ha ve been identified, including the 33/66-kD carboxyl-terminal heparin-b inding fragments, which support the adhesion of vascular endothelial c ells. A number of synthetic peptides representing amino acid sequences within the 33/66-kD fragments have been shown to promote the adhesion , spreading, and migration of a variety of cell types. Our working hyp othesis is that one or more of these sequences may also mediate vascul ar endothelial cell adhesion, spreading, and migration to the 33/66-kD fragments. In support of this hypothesis, we have demonstrated that e ndothelial cells from various sources adhered in a concentration-depen dent manner to surfaces coated with FN, the 33/66-kD fragments, and sy nthetic peptides derived from the 33/66-kD fragments of FN. FN and the 33/66-kD fragments also promoted endothelial cell spreading and migra tion. Although each of the six synthetic peptides tested supported end othelial cell adhesion, only one of these peptides within the carboxyl -terminal heparin-binding domain (FN-C/H-V) promoted endothelial cell spreading and migration. Cell spreading on FN-CM-V, as well as on FN a nd the 33/66-kD fragments, was associated with the formation of a well -developed actin cytoskeleton and the formation of focal contacts. FN- C/H-V (but not scrambled FN-C/H-V) inhibited cell spreading on FN and the 33/66-kD fragments in a concentration-dependent manner. FN-C/H-V h ad a modest effect on the adhesion of a clonal population of rat heart endothelial cells (RHE-1A) to the 33/66-kD fragments of FN and no eff ect on RHE-1A cell adhesion to FN. These findings suggest that peptide FN-C/H-V is unique among this group of peptides derived from the 33/6 6-kD heparin-binding fragments of FN in its ability to promote the adh esion, spreading, and migration of vascular endothelial cells and furt her suggest that the sequence defined by this peptide plays an importa nt role in vascular endothelial cell interactions with the 33/66-kD fr agments of FN.