Peptide amphiphile nanostructure–heparin interactions and their relationship to bioactivity

Abstract

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.

Controlled Delivery of Transforming Growth Factor β1 by Self-Assembling Peptide Hydrogels Induces Chondrogenesis of Bone Marrow Stromal Cells and Modulates Smad2/3 Signaling

“…26,30 These peptides can also control the delivery and release of functional proteins, 21 therapeutic macromolecules, 22 and bioactive motifs. 20 Taken together, these studies suggest the potential to co-encapsulate growth factors and BMSCs in self-assembling peptide hydrogels to generate cartilage neotissue.…”

“…[20][21][22][23][24] Benefits have been demonstrated for the use of these peptide hydrogels in cartilage, 25,26 liver, 27 and cardiovascular 28,29 tissues, and they have been shown to provide a microenvironment that enhances the chondrogenesis of BMSCs. 26,30 These peptides can also control the delivery and release of functional proteins, 21 therapeutic macromolecules, 22 and bioactive motifs.…”

Self‐Assembling Peptides as Cell‐Interactive Scaffolds

“…the peptide matrix. In one report by the Stupp laboratory, FGF2 and VEGF were bound to heparin binding peptide amphiphile (HBPA) nanofibers to promote angiogenesis (Figure 8) [70,72,73] The HBPA nanofiber gels were demonstrated to persist in vivo for up to 30 days and exhibited excellent biocompatibility. [74] After incorporation of FGF2 and VEGF, the HBPA nanofiber provided sustained release of the growth factors for 14 days in media.…”

Self-Assembled Peptides: Characterisation and In Vivo Response

“…Whole proteins have been incorporated into SAP scaffolds: permanently through the use of hydrophobic fibrils to allow stable inclusion of whole basement membrane proteins [23]; or temporarily, utilising the electrostatic interactions of charged residues, producing zero order slow release system [40]. Peptide amphiphile systems have been shown to self-assemble in the presence of, and subsequently actively bind, heparin through the inclusion of a heparin binding motif, whilst retaining its bioactivity [41]. In order to avoid the problems associated with the use of biologically derived whole proteins, some bioactive peptide sequences from oligopeptides have been utilised to engineer SAP scaffolds, such as LAIKNDNLVYVY to shorter motifs such as IKVAV, and RGD [42].…”