Promoted Aggregation of Aβ on Lipid Bilayers in an Open Flowing System.

Abstract

Self-assembly of amyloid-β (Aβ) peptides in nonequilibrium, flowing conditions is associated with pathogenesis of Alzheimer's disease. We examined the role of biologically relevant, nonequilibrium, flowing conditions in the desorption, diffusion, and integration of Aβ-lipid assemblies at the membrane surface using a microchannel connected with microsyringes. A 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) bilayer was formed on a glass substrate and incubated in Aβ solution under either a quiescent condition (no flow) or flowing condition for 24 h. Although dot-like aggregates (<1 μm) comprising Aβ fibrils formed on the DMPC membrane under the quiescent condition, larger plaque-like aggregates formed under the flowing condition, suggesting that nonequilibrium continuous flow governs the cytotoxicity of Aβ species. We propose that Aβ adsorption on the membrane surface involves spontaneous desorption of Aβ-lipid to form self-assembling aggregates, with this accelerated by surface shear forces. These findings suggest that nonequilibrium, flowing conditions influence inter/intra-molecular Aβ-fibril formation to trigger formation of amyloid plaques.