Amyloid fibrils adopt a range of morphologies, called structural polymorphs, that impact neurodegenerative disease pathology. Unfortunately, there are no methods to produce recombinant fibrils with structures similar to those found in disease patients. Similarly, it is unclear what chemical and biological factors influence fibril structure in vitro and in vivo. The goal of our proposal is to leverage exogenous materials to produce specific fibril structures comprised of the Alzheimer’s disease (AD) relevant protein, Aβ1-40. Specifically, we will combine tunable surface chemistry with high throughput electron microscopy to generate and characterize specific fibril populations. Next, we will evaluate the toxicity of specific fibril structures in cell culture in addition to their biochemical characteristics to validate their potential disease relevance. Together, our results will provide mechanistic insight into the role of chemical and surface environments in controlling fibril structure, enable reproducible access to specific Aβ1-40 fibril structures, and facilitate hypothesis-driven research on the role of fibril polymorphism in AD pathology.

Directing amyloid-β structural polymorphism: Bridging the gap between amyloids found in vivo and in vitro

ACS Spring Meeting 2021

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.