(272c) Simulations Investigating the Structure and Dynamics of Nanomaterial-Amyloid Interactions

Amyloid self-assembled fibrils have been reported to play a key role in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s, Parkinson’s and type 2 diabetes. The interaction between amyloids and nanomaterial interfaces has been the focus of several studies due to the ability of nanomaterials to exhibit potential in inhibiting fibrillation, disaggregating, and clearing mature amyloids, e.g., Aβ amyloids linked to Alzheimer’s disease¹. Despite the importance of investigating these interactions to shed light into particular mechanisms of inhibition and/or disaggregation, there is limited knowledge on the interactions between the particular biomolecules and interfaces. This impedes our understanding of the potential amyloid inhibition and disaggregation mechanisms of particular amyloid-nanomaterial systems. In this study, we used molecular docking in combination with molecular dynamics simulations to investigate in-detail the structure and dynamics between modeled amyloid fibrils with a modeled carbon nanomaterial. Our studies uncovered the key interaction modes between modeled amyloid fibrils and the modeled carbon material, providing insights into the thermodynamically favorable modes, potentially leading to inhibition, as well as into a portion of modes leading to biomolecular conformational changes, and partial dissociation of the simulated fibrils; the latter could be potentially associated with disaggregation properties. Our simulations comply with experimental findings associated with the amyloids studied with the corresponding carbon nanomaterial, and provide highly-detailed analysis, enlightening our understanding on the key interactions and their potential relation to the carbon-based modulation properties onto the amyloid fibrils. We consider that our findings could pave the way for novel anti-amyloid strategies.

1. Shao X et al. Nanoscale Adv. 2022;5(1):46-80.