Characterization of Peptide−Amphiphiles Possessing Cellular Activation Sequences

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Abstract
Numerous approaches have been described for modifying biomaterials to incorporate extracellular matrix components. “Peptide−amphiphiles”, whereby monoalkyl hydrocarbon chains are covalently linked to peptide sequences, have been shown previously to (a) form specific molecular architecture with enhanced stability and (b) promote cell adhesion, spreading, and signaling. The present study has examined the use of chimeric peptide−amphiphiles for inducing protein-like structures and peptide−amphiphile mixtures for enhancing surface bioactivity. The α-helical propensity of a 21 residue peptide, incorporating the SPARC119-122 angiogenesis-inducing sequence and either unmodified or acylated with a C6, C10, C14, C16, C18, C18:1, or C18:1-OH monoalkyl hydrocarbon chain, has been examined. Peptide and peptide−amphiphile structures were characterized by circular dichroism and one- and two-dimensional NMR spectroscopic techniques. The 21 residue peptide alone does not form a distinct structure in solution, whereas N-terminal acylation by monoalkyl hydrocarbon chains results in the 21 residue peptide−amphiphile adopting a predominantly α-helical structure in solution. The thermal stability of the α-helix increases with increasing hydrocarbon chain length. The SPARC119-122 peptide−amphiphiles were then screened for promotion of endothelial cell adhesion and spreading. The greatest activity was achieved by using a mixture of the α-helical SPARC119-122 peptide−amphiphile, a triple-helical peptide−amphiphile incorporating the α2β1 integrin bindng site from type I collagen, and a pseudolipid. The pseudolipid is most likely required for a spatial distribution of the peptide−amphiphiles that allows for optimal cellular interactions. Overall, we have found that incorporation of bioactive sequences within peptide−amphiphiles results in the induction of an ordered structure of the bioactive sequence and that mixtures of peptide−amphiphiles can be used to promote endothelial cell behaviors comparable to extracellular matrix components.

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