Peptide amphiphile nanostructure-heparin interactions and their relationship to bioactivity.
Heparin-protein interactions are important in many physiological processes including angiogenesis, the growth of new blood vessels from existing ones. We have previously developed a highly angiogenic self-assembling gel, wherein the self-assembly process is triggered by the interactions between heparin and peptide amphiphiles (PAs) with a consensus heparin binding sequence. In this report, this consensus sequence was scrambled and incorporated into a new peptide amphiphile in order to study its importance in heparin interaction and bioactivity. Heparin was able to trigger gel formation of the scrambled peptide amphiphile (SPA). Furthermore, the affinity of the scrambled molecule for heparin was unchanged as shown by isothermal titration calorimetry and high Förster resonance emission transfer efficiency. However, both the mobile fraction and the dissociation rate constant of heparin, using fluorescence recovery after photobleaching, were markedly higher in its interaction with the scrambled molecule implying a weaker association. Importantly, the scrambled peptide amphiphile-heparin gel had significantly less angiogenic bioactivity as shown by decreased tubule formation of sandwiched endothelial cells. Hence, we believe that the presence of the consensus sequence stabilizes the interaction with heparin and is important for the bioactivity of these new materials.
Rajangam
Kanya
K
Department of Biomedical Engineering, Northwestern University, Evanston, IL 60208, United States.
Arnold
Michael S
MS
Rocco
Mark A
MA
Stupp
Samuel I
SI
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects; D036681:Fluorescence Recovery After Photobleaching; D006493:Heparin / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D046911:Macromolecular Substances; D008422:Materials Testing; D046529:Microscopy, Electron, Transmission; D008958:Models, Molecular; D049329:Nanostructures / Q000008:administration & dosage / Q000737:chemistry / Q000648:ultrastructure; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009842:Oligopeptides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D013501:Surface-Active Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*
D046911:Macromolecular Substances; D009842:Oligopeptides; D013501:Surface-Active Agents; D006493:Heparin