Self-assembled peptide architectures for cell adhesion and drug delivery

There is significant interest in the development of biomaterials that can direct cellular response. This is often achieved by incorporation of peptides that can trigger biological events due to their specific recognition by cellular receptors. In order to maximize the response, efficient peptide presentation is required. The immobilization method selected must ensure that peptides retain their structure and activity, are displayed at sufficiently high density, and in an accessible fashion. This can be especially difficult when multiple peptides are required to produce a synergistic response. One powerful approach to achieve the above is the use of self-assembly of 'peptide amphiphiles'. Peptide amphiphiles consist of a peptide head-group conjugated to a hydrophobic 'tail' segment. Hydrophobic interactions drive self-assembly into a variety of structures, ranging from planar bilayers to spheroidal micelles, depending on molecular geometry and intermolecular interactions. Further, multi-functional aggregates of controlled composition can be created simply by appropriate mixing of monomers prior to self-assembly.;This thesis focused on the creation of multi-functional, peptide-based assemblies in two and three dimensions. One goal was the development of a facile method to present peptide ligands on surfaces. This was achieved by incorporating peptide amphiphiles into solid-supported planar lipid bilayers using vesicle fusion techniques. The resulting peptide-functionalized bilayers were then tested as substrates for cell adhesion. Adhesion and proliferation of fibroblast cells on RGD-modified bilayers was studied as a function of peptide density and accessibility in a high-throughput manner. The insight gained from this study was applied to the development of a surface that could support adhesion and self-renewal of neural stem cells, while retaining their potential to differentiate into neurons and astrocytes. The second part of this thesis dealt with the physico-chemical characterization of peptide amphiphile micelles, which are being developed for applications in targeted drug delivery. The stability of these micelles was shown to increase significantly upon transition of the lipid core into a condensed, glassy phase at low temperatures. This finding can be used to tailor the stability of micellar nanoparticles for improved in vivo drug delivery.