Effect of RGD secondary structure and the synergy site PHSRN on cell adhesion, spreading and specific integrin engagement

Sarah E. Ochsenhirt, Efrosini Kokkoli, James B. McCarthy, Matthew Tirrell

Research output: Contribution to journalArticlepeer-review

110 Scopus citations


The relationship between the form of cell adhesion, ligand presentation, and cell receptor function was characterized using model Langmuir-Blodgett supported films, containing lipid-conjugated peptide ligands, in which isolated variables of the ligand presentation were systematically altered. First, the conformation of an adhesive Arginine-Glycine-Aspartic acid (RGD) peptide was varied by synthesizing linear and looped RGD peptide-containing amphiphiles and subsequently measuring the impact on the function of human umbilical vein endothelial cells. Secondly, the contribution of non-contiguous ligands to cellular engagement was assessed using multi-component biomimetic films. The peptide amphiphiles were composed of fibronectin-derived headgroups-GRGDSP, and its synergy site Pro-His-Ser-Arg-Asn (PHSRN)-attached to hydrocarbon tails. The peptide amphiphiles were diluted using polyethylene glycol (PEG) amphiphiles, where PEG inhibited non-specific cell adhesion. Cells adhered and spread on GRGDSP/PEG systems in a dose-dependent manner. The presentation of GRGDSP influenced integrin cell surface receptor specificity. Results demonstrated that β1-containing integrins mediated adhesion to the linear GRGDSP presentation to a greater extent than did the αvβ3 integrin, and looped GRGDSP preferentially engaged αvβ3. GRGDSP/PHSRN/PEG mixtures that closely mimicked the RGD-PHSRN distance in fibronectin, enhanced cell spreading over their two-component analogues. This study demonstrated that controlling the microenvironment of the cell was essential for biomimetics to modulate specific binding and subsequent signaling events.

Original languageEnglish (US)
Pages (from-to)3863-3874
Number of pages12
Issue number20
StatePublished - Jul 2006

Bibliographical note

Funding Information:
This work was partially supported by the MRSEC Program of the National Science Foundation under Award no. DMR00-80034 at the University of California, Santa Barbara and partially by the University of Minnesota MRSEC Artificial Tissues Program (DMR99-09364).


  • Cyclic RGD
  • Looped RGD
  • α5β1 integrin
  • αβ integrin


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