Biomimetic peptide-amphiphiles for functional biomaterials: The role of GRGDSP and PHSRN

The study we present involves the use of a biomimetic system that allows us to study specific interactions in the α₅β ₁ receptor-GRGDSP ligand system with an atomic force microscope (AFM). Bioartificial membranes that mimic the adhesion domain of the extracellular matrix protein fibronectin are constructed from peptide-amphiphiles. A novel peptide-amphiphile is designed that contains both GRGDSP (Gly-Arg-Gly-Asp-Ser-Pro, the primary recognition site for α₅β₁) and PHSRN (Pro-His-Ser-Arg-Asn, the synergy binding site for α ₅β₁) sequences in a single peptide formulation, separated by a spacer. Two different antibodies are used to immobilize and activate isolated α₅β₁ integrins on the AFM tip. The interaction measured between immobilized α₅β₁ integrins and peptide-amphiphiles is specific for integrin-peptide binding and is affected by divalent cations in a way that accurately mimics the adhesion function of the α₅β₁ receptor. The strength of the PHSRN synergistic effect depends on the accessibility of this sequence to α₅β₁ integrins. An increase in adhesion is observed compared to surfaces displaying only GRGDSP peptides when the new biomimetic peptide-amphiphiles are diluted with lipidated poly(ethylene glycol), which provides more space for the peptide headgroups to bend and expose more of the PHSRN at the interface.