Date of Award

1-1-2012

Language

English

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

College/School/Department

Department of Chemistry

Content Description

1 online resource (xiii, 100 pages) : illustrations (some color)

Dissertation/Thesis Chair

Igor K Lednev

Committee Members

Laurence A Nafie, Daniele Fabris, Li Niu, Alexander Shekhtman

Keywords

amyloid, chirality, fibrils, polymorphs, Amyloid beta-protein, Protein folding, Chirality, Raman spectroscopy

Subject Categories

Analytical Chemistry | Biochemistry | Chemistry

Abstract

Specific protein aggregation has been linked to more than 25 severe human maladies including prion, Alzheimer's, and Parkinson's diseases. These important malfunctions are often referred to as 'conformational' disorders and result from the conversion of a normal isoform of a protein into a specific b-sheet rich polymeric amyloid form. This work elaborates a comprehensive characterization of amyloids and dedicated to the investigation of the fibril polymorphism using advanced microscopic tools, such as Atomic Force and Scanning Electron microcopies, together with several vibrational spectroscopy techniques, such as Raman, Infrared and Vibrational Circular Dichroism. A new type of protein folding-aggregation phenomenon, spontaneous refolding of amyloid fibrils from one polymorph to another, was discovered. The phenomenon was demonstrated for two different proteins and two different stimuli. This discovery is significant because it opens a potential opportunity to control the biological activity and associated toxicity of amyloid fibrils.

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