Nanofiber Formation by Collagen Mimetic Peptides: Elucidation of Supramolecular Principles and Application of Retrosynthetic Analysis
Hartgerink, Jeffrey D.
Doctor of Philosophy
Synthetic mimics of the fibrillar protein collagen were designed by engineering specific supramolecular interactions in the triple helical building blocks. My doctoral research indicates that tri-domain collagen mimetic peptides, with positive, neutral, and negative domains, may form nanofibrous assembly through a staggered triple-helical intermediate stabilized by inter-strand charge pairs. Based on our understanding of the fibrillation pathway, I have devised a supramolecular retrosynthetic strategy to prepare collagen mimetic nanofibers. By designing an infinite triple helix with optimal number of inter-strand charge pairs, and then identifying the requisite building blocks, I was able to prepare a two-component collagen mimetic fiber with a high melting temperature. Peptide-based collagen mimetic nanofibers have great potential for future medical applications.