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A Chemical, Structural and Biophysical Exploration into the Nanoscale Properties of Amyloid Fibrils

Beal, David (2016) A Chemical, Structural and Biophysical Exploration into the Nanoscale Properties of Amyloid Fibrils. Doctor of Philosophy (PhD) thesis, University of Kent.

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Abstract

Amyloid structures have been identified as a key pathological marker in a range of conditions such as Alzheimer’s and Parkinson’s disease. A combination of their disease relevance and potential nanomaterial applications has made understanding amyloid formation and the source of its toxicity of great interest. The fragmentation of amyloid fibrils into smaller particles is important for the kinetics of their formation and how they elicit toxicity. This thesis sheds light on how fibrils formed from different proteins fragment, and compares their resistance to mechanical stress, in order to decipher if fibril fragmentation mechanism is fibril dependent or a property shared by amyloid fibrils in general. To accomplish these goals, this thesis is divided into three sections.

The second part investigates the resistance to mechanical stress of ?-synuclein, ?-lactoglobulin and lysozyme fibrils using a fragmentation assay, which enables the determination and comparison of the fibrils’ resistance to mechanical stress. This work has demonstrated that polymer rigidity (Lp) is inherently linked to the resistance of the tested amyloid fibrils to mechanical stress.

The third part of the thesis successfully implements a chemical labelling strategy using ‘click’ chemistry to allow a modification of fibril functionality. This has been applied to fluorescence labelling strategies and 19F-labelling for novel methods of determining the population size of amyloid fibrils by 19F DOSY NMR.

Item Type: Thesis (Doctor of Philosophy (PhD))
Thesis advisor: Xue, Wei-Feng
Thesis advisor: Tuite, Mick
Uncontrolled keywords: Amyloid
Subjects: Q Science
Divisions: Faculties > Sciences > School of Biosciences
Depositing User: Users 1 not found.
Date Deposited: 31 Mar 2016 09:26 UTC
Last Modified: 24 Jan 2020 04:08 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/54750 (The current URI for this page, for reference purposes)
Beal, David: https://orcid.org/0000-0002-1819-315X
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