Peptides derived from fibronectin type III connecting segments promote endothelial cell adhesion but not platelet adhesion: implications in tissue-engineered vascular grafts.
The development of a completely tissue-engineered small-caliber prosthesis suitable for incorporation into an in vivo vascular network is fraught with many challenges, including overcoming resistance to endothelialization and susceptibility to thrombogenesis. In this work, recombinant human fibronectin-derived low-molecular-weight peptide fragments were studied for their ability to promote cell type-specific alpha(4) integrin-mediated adhesion. Two populations of primary human endothelial cells were examined and found to express alpha(4) integrin receptors on their surfaces; on the contrary, human platelets were not found to be expressers of alpha(4) integrins. A peptide fragment isolated from the variably spliced human fibronectin type III connecting segment-1 (CS-1) domain was determined to mediate statistically significant endothelial cell alpha(4) integrin-mediated adhesion. In contrast, the fibronectin type III CS-1 fragment did not support human platelet adhesion under physiological fluid shear conditions, although fully intact human fibronectin molecules supported shear-induced platelet adhesion. This suggests that platelets bind to fibronectin in regions not encompassing the CS-1 domain. In conclusion, this work has demonstrated that the low-molecular-weight peptide CS-1 could serve as a cell-selective adhesion mediator in the engineering of a more-compatible small-caliber vascular graft lumen interface.
Rodenberg
Eric J
EJ
Department of Cellular and Integrative Physiology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA.
Pavalko
Fredrick M
FM
D000595:Amino Acid Sequence; D002448:Cell Adhesion / Q000187:drug effects; D018929:Cell Culture Techniques / Q000379:methods; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology; D003470:Culture Media; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000166:cytology; D005353:Fibronectins / Q000737:chemistry*; D006801:Humans; D039441:Integrin alpha4 / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000494:pharmacology*; D010973:Platelet Adhesiveness / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000494:pharmacology; D013314:Stress, Mechanical; D023822:Tissue Engineering / Q000379:methods*; D014471:Umbilical Veins / Q000166:cytology
D003470:Culture Media; D005353:Fibronectins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D039441:Integrin alpha4