Study of a Self-assembling Polypeptide Nanotube: Structure, Dynamics and Applications in Cancer and Tissue engineering

Abstract

This thesis contains five chapters addressing the characterization and applications of a self-assembled polypeptide nanotube. It starts with an introduction to protein-based self-assembly and RGD-based targeted approaches in cancer. The formation and characterization of self-assembled nanotubes of a polypeptide fragment (hIGFBP2-249-289) is described in the second chapter, followed by a description of the structural insights and capturing intermediates of self-assembling nanotubes obtained using protein-NMR techniques in the third chapter. The fourth and fifth chapters focus on the RGD-based biomedical applications of nanotubes in cancer therapeutics and tissue engineering. An exhaustive literature has established that the ‘‘RGD’’, the adhesive peptide, is incorporated in a variety of biomaterials and shown to be highly effective in promoting the adhesion, morphology, and migration of numerous cell types to the plethora of diverse materials. Towards this end, we evaluated the effect of RGD containing hIGFBP-2249-289 nanotubes on different cell types. The presence of multi-RGD array on these nanotubes renders them the potential for using in tissue engineering. The proliferation and adhesion profiles of fibrosarcoma cells were examined when treated with nanotubes. The migration of epithelial cells and spreading of the fibroblast were observed significant when treated with nanotubes. Results confirm the functionality of RGD motif in these nanotubes. Taken together, the preparation and characterization of nanotubes have been described, the details of structure and dynamics of nanotubes examined and the utility of hIGFBP-2249-289 nanotubes in cancer therapeutics and tissue engineering.