Comparative cell response to artificial extracellular matrix proteins containing the RGD and CS5 cell-binding domains.
This study addresses endothelial cell adhesion and spreading on a family of artificial extracellular matrix (aECM) proteins designed for application in small-diameter vascular grafts. The aECM proteins contain domains derived from elastin and from fibronectin. aECM 1 contains the RGD sequence from the tenth type III domain of fibronectin; aECM 3 contains the fibronectin CS5 cell-binding domain. Negative control proteins aECM 2 and 4 are scrambled versions of aECM 1 and 3, respectively. Competitive peptide inhibition studies and comparisons of positive and negative control proteins confirm that adhesion of HUVECs to aECM proteins 1 and 3 is sequence specific. When subjected to a normal detachment force of 780 pN, 3-fold more HUVECs remained adherent to aECM 1 than to aECM 3. HUVECs also spread more rapidly on aECM 1 than on aECM 3. These results (i) indicate that cellular responses to aECM proteins can be modulated through choice of cell-binding domain and (ii) recommend the RGD sequence for applications that require rapid endothelial cell spreading and matrix adhesion.
Division of Chemistry and Chemical Engineering, California Institute of Technology, Mail Code 210-41, Pasadena, California 91125, USA.
Julie C
JC
Liu
Sarah C
SC
Heilshorn
David A
DA
Tirrell
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000138:chemical synthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology
D016326:Extracellular Matrix Proteins; D009842:Oligopeptides; D010455:Peptides; C067467:CS5 peptide; C047981:arginyl-glycyl-aspartic acid