Multidomain Peptides: Sequence-Nanostructure Relationships and Biological Applications
Bakota, Erica Laraine
Hartgerink, Jeffrey D.
Doctor of Philosophy
Peptides are materials that, as a result of their polymeric nature, possess enormous versatility and customizability. Multidomain peptides are a class of peptides that selfassemble to form stable, cytocompatible hydro gels. They have an ABA block motif, in which the A block is composed of charged amino acids, such as lysine, and the B block consists of alternating hydrophilic and hydrophobic amino acids, such as glutamine and leucine. The B block forms a facial amphiphile that drives self-assembly. The charged A blocks simultaneously limit self-assembly and improve solubility. Self-assembly is triggered by charge screening of these charged amino acids, enabling the formation of ~sheet fibers. The development of an extended nanofiber network can result in the formation of a hydrogel. Systematic modifications to both the A and B blocks were investigated, and it was found that sequence modifications have a large impact on peptide nanostructure and hydrogel rheology. The first modification examined is the substitution of amino acids within the hydrophilic positions of the B block. The second set of modifications investigated was the incorporation of aromatic amino acids in the B block. Finally, the charged block was varied to generate different net charges on the peptides, a change which impacted the ability to use these peptides in cell culture. Two applications of multi domain peptide nanofibers are explored, the first of which is the delivery of novel therapies in vivo. One multidomain peptide is able to form hydrogels that undergo shear-thinning and rapid recovery. This gel can be loaded with cytokines and growth factors that have been secreted by embryonic stem cells, and these molecules can be subsequently released in a therapeutic setting. Another application for multidomain peptide is their use as biocompatible surfactants. Single-walled carbon nanotubes have been widely investigated for their unique optical and electrical properties, but their solubility in aqueous systems has been a challenge. Multidomain peptides solubilize carbon nanotubes, are less cytotoxic than detergents such as SDBS, and preserve the ability of carbon nanotubes to fluoresce. Some of these peptides are also compatible with cell culture, allowing the delivery of single-walled carbon nanotubes to cells.