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

A biomembrane-related fibrillogenesis of Amyloid ß from Alzheimer' disease (Aß) is closely related to its accumulation behavior. A binding property of Aß 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 Aß, Δfmax, was determined from the measurement of the maximal frequency reduction using QCM. The plots of Δfmax to Aß concentration gave the slope and saturated value of Δfmax, (Δfmax)sat that are the parameters for binding property of Aß to lipid membranes. Therefore, the Aß-binding property on lipid membranes was classified by the slope and (Δfmax)sat. The plural lipid system was described as X + Y where X = L1, L1/L2, and L1/L2/L3. The slope and (Δfmax)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 Aß-specific binding site, generated at the boundary between ld and lo phases. The LP violation observed only in the slope resulted from glycolipid-rich domain acting as Aß-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 Aß binding property on lipid membranes appeared to be related to the fibrillogenesis with a certain morphology.

ToF-SIMS analysis of amyloid beta aggregation on different lipid membranes.

Amyloid beta (Aß) peptides are considered to be strongly related to Alzheimer's disease. Aß peptides form a ß-sheet structure on hard lipid membranes and it would aggregate to form amyloid fibrils, which are toxic to cells. However, the aggregation mechanism of Aß is not fully understood. To evaluate the influence of the lipid membrane condition for Aß aggregation, the adsorption forms of Aß (1-40) on mixture membranes of lipid 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol ß-d-glucoside (ß-CG) were investigated by time-of-flight secondary ion mass spectrometry. As a result, Aß adsorbed along the localized DMPC lipid on the mixture lipid membranes, whereas it was adsorbed homogeneously on the pure DMPC and ß-CG membranes. Moreover, amino acid fragments that mainly existed in the n-terminal of Aß (1-40) peptide were strongly detected on the localized DMPC region. These results suggested that the Aß was adsorbed along the localized DMPC lipid with a characteristic orientation. These findings suggest that the hardness of the membrane is very sensitive to coexisting materials and that surface hardness is important for aggregation of Aß.