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.
Liu
Julie C
JC
Division of Chemistry and Chemical Engineering, California Institute of Technology, Mail Code 210-41, Pasadena, California 91125, USA.
Heilshorn
Sarah C
SC
Tirrell
David A
DA
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