Self-Assembly of Repeat Block Copolypeptides

Chilkoti, Ashutosh

Weitzhandler, Isaac

2018-03-20T17:53:40Z

2019-08-29T08:17:12Z

2017

Biomedical Engineering

Self-assembling polypeptides such as elastin-like polypeptides are already used extensively for drug delivery and other applications. However, the current generation of polypeptide drug delivery vehicles was engineered and selected based on a phenomenological rather than molecular-level understanding of polypeptide self-assembly. In order to rationally design the next generation of self-assembling polypeptide drug delivery vehicles, it is necessary to develop a deeper understanding of the rules governing self-assembly.

This work consists of the synthesis of systematically designed families of recombinant polypeptides and their characterization using nanoscale soft-matter characterization techniques. Block copolypeptides synthesized were based on elastin-like and resilin-like polypeptides, and formed a range of micelles, highly ordered bulk phases, and surface self-assemblies. Polypeptide phase-behavior and self-assembly were characterized by thermal turbidimetry, light scattering, small angle scattering (X-ray and neutron), and cryogenic transmission electron microscopy. This systematic synthesis of polypeptides coupled with detailed characterization allowed for a deeper, molecular-level understanding of the forces governing polypeptide self-assembly, which in turn will inform (and in fact has already informed) the future use of self-assembling polypeptides as drug delivery vehicles.

https://hdl.handle.net/10161/16249

Biomedical engineering

biomolecular engineering

block copolymer

repeat polypeptides

Self-assembly

Self-Assembly of Repeat Block Copolypeptides

Dissertation

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