Classification of binding property of amyloid β to lipid membranes: Membranomic research using quartz crystal microbalance combined with the immobilization of lipid planar membranes

Abstract

A biomembrane-related fibrillogenesis of Amyloid β from Alzheimer' disease (Aβ) is closely related to its accumulation behavior. A binding property of Aβ peptides from Alzheimer' disease to lipid membranes was then classified by a quartz crystal microbalance (QCM) method combined with an immobilization technique using thiol self-assembled membrane. The accumulated amounts of Aβ, Δf_max, was determined from the measurement of the maximal frequency reduction using QCM. The plots of Δf_max to Aβ concentration gave the slope and saturated value of Δf_max, (Δf_max)^sat that are the parameters for binding property of Aβ to lipid membranes. Therefore, the Aβ-binding property on lipid membranes was classified by the slope and (Δf_max)^sat. The plural lipid system was described as X + Y where X = L₁, L₁/L₂, and L₁/L₂/L₃. The slope and (Δf_max)^sat values plotted as a function of mixing ratio of Y to X was classified on a basis of the lever principle (LP). The LP violation observed in both parameters resulted from the formation of the crevice or pothole, as Aβ-specific binding site, generated at the boundary between l_d and l_o phases. The LP violation observed only in the slope resulted from glycolipid-rich domain acting as Aβ-specific binding site. Furthermore, lipid planar membranes indicating strong LP violation favored strong fibrillogenesis. Especially, lipid planar membranes indicating the LP violation only in the slope induced lateral aggregated and spherulitic fibrillar aggregates. Thus, the classification of Aβ binding property on lipid membranes appeared to be related to the fibrillogenesis with a certain morphology.

Keywords: Alzheimer's disease; Amyloid β peptide; Glycolipid; Lever principle; Phospholipids; Quartz crystal microbalance.