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Title: Nucleation and growth of insulin fibrils in bulk solution and at hydrophobic surfaces
Author: Smith, Michael
Awarding Body: University of Nottingham
Current Institution: University of Nottingham
Date of Award: 2008
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The formation of amyloid fibrils and their associated aggregates has important. applications in the understanding of among others, Alzheimer's disease and Huntingdon's disease. In this study FTIR spectroscopy, together with complimentary techniques, was used to investigate the nucleation and growth of insulin fibrils in bulk solution and at a polystyrene interface. Fibril nucleation rates were fonnd to be significantly enhanced by the presence of a polystyrene surface when compared with the bulk. However, growth rates at a polystyrene surface were found to be significantly slower than those observed in the bulk. The energy barriers to nucleation and growth of fibrils in bulk solution were found to be 117 ± 2kJMoZ-1 and 72 ± 10kJMoZ-1 respectively. The corresponding values measured for fibril formation at a polystyrene surface were 119 ± 11kJMoZ-1 and 120 ± 14kJMoZ- I • Fibril formation was shown to be preceded by the formation of a small rv 13mn aggregate which contains a small amount of intermolecular J3-sheet. Experimental evidence is presented that this prefibrillar aggregate represents a necessary precursor to fibril nucleus formation. The growth of insulin amyloid spherulites was also studied using time lapse optical microscopy. 1Ieasurement of the growth rates of spherulites at different temperatures enabled the energy barriers to nucleation and growth to be calculated. Comparison of fibril and spherulite energy barriers showed no difference within error. A side project studying the formation of regular crack patterns in thin films of drying colloidal particles was also pursued. It was found that contrary to expectation the particle size had no effect on the cracking lengthscale oyer the entire range of film thicknesses studied (5 - 200/lm). Experimental evidence is presented that shows it is the constraint provided by the substrate that leads to crack formation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available