Binding and Membrane Damage Behaviors of Self-Aggregated Beta-Amyloid Oligomers on Lipid Raft Surfaces from Microsecond Molecular Dynamics Simulations

Our hypothesis is that self-aggregated Beta-Amyloid Oligomers can bind to phase-separated lipid nanodomains and damage the membrane structures. The data were generated by microsecond molecular dynamics simulations of the binding events of beta-amyloid oligomers to phase-separated lipid rafts with or without glycolipid clusters, i.e., GM-raft or CO-raft. The lipid domain preference and binding energies of disordered amyloid aggregate to highly dynamic and heterogeneous lipid bilayers in structurally specific lipid nanodomains, e.g., glycolipid-clusters, cholesterol-enriched liquid-ordered (Lo) or cholesterol-depleted liquid-disordered (Ld), or mixed Lo/Ld (Lod) region, and annular lipid shells surrounding the membrane-bound protein, provide helpful insight into guiding future experiments to understand the regulation of lipid composition and structures on amyloid binding to cell membranes. The information is also helpful for the design of drug interventions and novel imaging markers targeting membrane-bound amyloidogenic oligomers. The results will guide the new design of single-molecule experiments aiming at understanding amyloidogenic proteins binding to complex but realistic lipid membranes, containing multiple lipid components and varying domain sizes and structures. The details of the procedures of modeling and simulations of beta-amyloid oligomers in lipid rafts have been described in a research article by Pham, T. and K.H. Cheng, Exploring the Binding Kinetics and Behaviors of Self-Aggregated Beta-Amyloid Oligomers to Phase-Separated Lipid Rafts with or without Ganglioside-Clusters. Biophysical Chemistry, 2022. (https://www.sciencedirect.com/science/article/abs/pii/S0301462222001168)

This work has been supported by the Robert A. Welch Foundation [W-2057-20210327], National Science Foundation [OAC 153159], National Institutes of Health [RCC1GM090897], Williams Endowment for Interdisciplinary Physics and Murchison Undergraduate Research Fellowship of Trinity University.