Interactions of β-amyloid (Aβ) peptides with neuronal membranes have been associated with the pathogenesis of Alzheimer's disease (AD); however, the molecular details remain unclear. We used atomistic molecular dynamics (MD) simulations to study the interactions of Aβ40 and Aβ42 with model neuronal membranes. The differences between cholesterol-enriched and depleted lipid domains were investigated by the use of model phosphatidylcholine (PC) lipid bilayers with and without 40 mol % cholesterol. A total of 16 independent 200 ns simulation replicates were investigated. The surface area per lipid, bilayer thickness, water permeability barrier, and lipid order parameter, which are sensitive indicators of membrane disruption, were significantly altered by the inserted state of the protein. We conclude that cholesterol protects Aβ-induced membrane disruption and inhibits β-sheet formation of Aβ on the lipid bilayer. The latter could represent a two-dimensional (2D) seeding template for the formation of toxic oligomeric Aβ in the pathogenesis of AD.
Document Object Identifier (DOI)
Qiu, L., Buie, C., Reay, A., Vaughn, M. W., & Cheng, K. H. (2011). Molecular dynamics simulations reveal the protective role of cholesterol in β-amyloid protein-induced membrane disruptions in neuronal membrane mimics. Journal of Physical Chemistry B, 115, 9795-9812. doi: 10.1021/jp2012842
Journal of Physical Chemistry B