Soluble heparin-binding peptides regulate chemokinesis and cell adhesive forces.
The ability of a soluble heparin-binding peptide sequence derived from fibronectin 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 soluble heparin-binding peptide resulted in the disassembly of focal adhesions, as assessed by immunohistochemical staining. These observations were consistent with an observed dose-dependent two- to fivefold reduction in cell-substrate adhesive strength (P < 0.001) and a biphasic effect on migration speed (P < 0.05). Moreover, heparin-binding peptides induced a twofold reduction (P < 0.01) in two-dimensional cell dispersion in the presence of a non-heparin-binding growth factor, platelet-derived growth factor-AB (PDGF-AB). Heparin-binding peptides were unable to mediate these effects when cells were grown on substrates lacking a heparin-binding domain. These data support the notion that competitive interactions between cell surface heparan sulfates with heparin-binding peptides may modulate chemokinetic cell migration behavior and other adhesion-related processes.
Chon
J H
JH
School of Chemical Engineering, Georgia Institute of Technology, Atlanta, GA 30332, USA.
Chaikof
E L
EL
D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D022001:Focal Adhesions / Q000187:drug effects / Q000502:physiology; D006493:Heparin / Q000378:metabolism; D006497:Heparan Sulfate / Q000378:metabolism* / Q000494:pharmacology; D007457:Iodine Radioisotopes; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism* / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011651:Pulmonary Artery / Q000166:cytology; D051381:Rats; D012995:Solubility
D005353:Fibronectins; D006493:Heparin; D006497:Heparan Sulfate; D007457:Iodine Radioisotopes; D018696:Neuroprotective Agents; D010982:Platelet-Derived Growth Factor; C417707:fibronectin peptide V; C095477:platelet-derived growth factor AB