Soluble heparin-binding peptides regulate chemokinesis and cell adhesive forces

The ability of a soluble heparin-bindingpeptide sequence derived from fibronectin to modulate the adhesion andchemokinetic migration behavior of arterial smooth muscle cells wasassessed using a novel glass microsphere centrifugation assay andautomated time-lapse fluorescence videomicroscopy, respectively.Treatment of cells grown on fibronectin-coated substrates with thesoluble heparin-binding peptide resulted in the disassembly of focaladhesions, as assessed by immunohistochemical staining. Theseobservations were consistent with an observed dose-dependent two- tofivefold reduction in cell-substrate adhesive strength(P < 0.001) and a biphasic effect on migration speed(P < 0.05). Moreover, heparin-binding peptides induceda twofold reduction (P < 0.01) in two-dimensional celldispersion in the presence of a non-heparin-binding growth factor,platelet-derived growth factor-AB (PDGF-AB). Heparin-binding peptideswere unable to mediate these effects when cells were grown onsubstrates lacking a heparin-binding domain. These data support thenotion that competitive interactions between cell surface heparansulfates with heparin-binding peptides may modulate chemokinetic cellmigration behavior and other adhesion-related processes.