Year

2019

Degree Name

Doctor of Philosophy

Department

Australian Institute for Innovative Materials

Abstract

Alzheimer’s disease (AD) has recently been labelled the ‘twenty-first century plaque’ and it has been estimated that more than 40 million people around the world suffer from this progressive disease. Within the amyloid hypothesis in Alzheimer’s disease, current focus has shifted to earlier stages of amyloid beta (Aβ) peptide assembly, involving soluble oligomers and smaller aggregates that are more toxic to cells compared to their morphological distinct fibril forms. Critical to the Aβ field is unlocking the molecular-level kinetic pathways or mechanisms of oligomerization, leading to the culprit subset or specific species of Aβ oligomer populations responsible for the disease etiology. However, since the protein aggregation is highly dynamic, involving temporally and kinetically controlled processes, and also very difficult to monitor in the early stages, a key challenge is understanding dynamic Aβ at the single molecule level under physiologically relevant conditions such as liquid.

Therefore, to probe the combined structural-dynamics of Aβ peptides, High-Speed Atomic Force Microscope (HS-AFM) was used, as it enables direct observation of single molecules at sub-molecular spatial resolution and with time resolution of up to 50milliseconds. For example, the main inventors of HS-AFM, Toshio Ando and his co-workers, produced realtime videos of the walking mechanism of a single Myosin V along an actin filament. Such movies existed before only as animations, but have now become reality due to the advent of HS-AFM. The thesis comprises 5 chapters, including introduction, 3 experimental and conclusion/future work...

This thesis is unavailable until Wednesday, May 05, 2021

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Unless otherwise indicated, the views expressed in this thesis are those of the author and do not necessarily represent the views of the University of Wollongong.