A von Willebrand factor-derived heparin-binding peptide regulates cell--substrate adhesive strength and chemokinesis behavior.
The ability of a soluble heparin-binding oligopeptide sequence derived from the von Willebrand factor (vWF) to modulate the adhesion and chemokinetic migration behavior of arterial smooth muscle cells was assessed using a novel glass microsphere centrifugation assay and automated time-lapse fluorescence videomicroscopy, respectively. Treatment of cells grown on fibronectin-coated substrates with the heparin-binding peptide resulted in the disassembly of focal adhesions, as assessed by immunohistochemical staining. These observations were consistent with six-fold decrease in cell--substrate adhesive strength (P<0.001), a biphasic effect on migration speed (P<0.05), as well as a dose-dependent reduction in the percentage of motile cells and the cell dispersion coefficient (mu=S(2)T/2). The specificity of this response to the vWF-derived heparin-binding peptide was supported by the absence of an observed effect in the presence of either a scrambled peptide or a consensus heparin-binding peptide sequence of similar heparin affinity. These data support the notion that competitive interactions between cell surface heparan sulfates with heparin-binding peptide domains located in soluble peptide fragments may modulate chemokinetic cell migration behavior and other adhesion-related processes.
Chon
John H
JH
Department of Surgery, Emory University, Atlanta, GA 30322, USA.
Chaikof
Elliot L
EL
D000818:Animals; D023181:Antimicrobial Cationic Peptides; D001667:Binding, Competitive; D001798:Blood Proteins / Q000737:chemistry / Q000494:pharmacology*; D002352:Carrier Proteins / Q000737:chemistry / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D015536:Down-Regulation; D005353:Fibronectins / Q000737:chemistry; D022001:Focal Adhesions / Q000187:drug effects; D006497:Heparan Sulfate / Q000737:chemistry; D018715:Microscopy, Video; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D014841:von Willebrand Factor / Q000737:chemistry*
D023181:Antimicrobial Cationic Peptides; D001798:Blood Proteins; D002352:Carrier Proteins; D005353:Fibronectins; D006497:Heparan Sulfate; D010455:Peptides; D014841:von Willebrand Factor; C062991:AZU1 protein, human