Date of Award
Doctor of Philosophy (PhD)
Materials Science and Engineering
Stephen H. Foulger
Ulf D. Schiller
Amyloids are the products of protein misfolding into fibril-like structures, which take place in human tissues and organs, including the human brain, heart, liver, and pancreas. As the deposition of amyloid fibrils usually leads to the dysfunction or death of cells, the formation of amyloid is associated with more than 20 human diseases, such as Alzheimer’s, Parkinson’s, and type 2 diabetes. Understanding how soluble peptides to form amyloid fibrils and how to modulate those amyloid aggregation are central to the design of rational therapeutic strategies against those diseases. Increasing experiments suggest that amyloid peptides can undergo liquid-liquid phase separation (LLPS) before the formation of amyloid fibrils. However, the exact role of LLPS in amyloid aggregation at the molecular level remains elusive. Here, the LLPS and amyloid fibrillization of a coarse-grained peptide, capable of capturing fundamental properties of amyloid aggregation over a wide range of concentrations was investigated in Discrete Molecular Dynamics (DMD) simulations. I also studied the different biomolecules and nanoparticles interactions with amyloid proteins. This study provides a unified picture of amyloid aggregation for a wide range of concentrations within the framework of LLPS and the potential mitigation of amyloid aggregations, which may help us better understand the etiology of amyloid diseases and disease therapist for human diseases.
Xing, Yanting, "Understanding and Modulating Amyloid Aggregation" (2021). All Dissertations. 2944.