Author

Satyam Singh

Date of Award

Summer 2021

Document Type

Open Access Thesis

Department

Chemistry and Biochemistry

First Advisor

F. Wayne Outten

Abstract

The iron-storage protein ferritin (Ftn) assembles into a protein cage structure with 24 subunits and octahedral (4-fold, 3-fold, 2-fold) symmetry. Each monomeric subunit contains a robust four-helix bundle fold. The fully assembled Ftn structure has a high degree of thermal stability (up to 100°C), a mono dispersed size (12 nm in diameter), and a large central cavity (7-8 nm in diameter). The central cavity stores ferric iron in phylogenetically diverse group of organisms, including humans. The central cavity has been used for encapsulation of cargoes such as other metals, contrast agents for imaging, small molecule drugs for therapy, as well as smaller nanoparticles. Ferritin has been widely used for several biomaterials, ranging from nanostructured composite materials to semiconductors to imaging reagents due to its attractive properties. Here we describe our initial efforts to design, generate, and test a series of pH-responsive derivatives of Ferritin (Ftn) protein nanocages that are competent for drug delivery through the endocytic pathway and may be helpful as responsive scaffolds for biomaterials construction. We plan to use a combination of analytical, biochemical, and biophysical techniques to characterize the Ftn derivates, thereby providing new insight into the principles for engineering bio-macromolecular assemblies for stimuli responsiveness.

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