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

Self-assembly of amyloid-beta (A beta) 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 A beta-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 A beta solution under either a quiescent condition (no flow) or flowing condition for 24 h. Although dot-like aggregates (<1 mu m) comprising A beta fibrils formed on the DMPC membrane under the quiescent condition, larger plaque-like aggregates formed under the flowing condition, suggesting that non-equilibrium continuous flow governs the cytotoxicity of A beta species. We propose that A beta adsorption on the membrane surface involves spontaneous desorption of A beta-lipid to form self-assembling aggregates, with this accelerated by surface shear forces. These findings suggest that nonequilibrium, flowing conditions influence inter/intra-molecular A beta-fibril formation to trigger formation of amyloid plaques.

Automated summary

The study showed that under nonequilibrium, flowing conditions, larger plaque-like aggregates of Aβ peptides formed on the membrane surface, potentially accelerated by surface shear forces, influencing the intra/intermolecular formation of Aβ-fibrils and triggering the formation of amyloid plaques.