Iida-Adachi Akane, Nabika Hideki
Department of Science, Graduate School of Science and Engineering, Yamagata University, 1-4-12, Kojirakawa, Yamagata 990-8560, Japan.
Faculty of Science, Yamagata University, 1-4-12, Kojirakawa, Yamagata 990-8560, Japan.
Langmuir. 2025 Feb 11;41(5):3121-3129. doi: 10.1021/acs.langmuir.4c03663. Epub 2025 Jan 30.
The aggregation and accumulation of amyloid β 42 (Aβ42) peptides on the surface of brain cells is associated with Alzheimer's disease (AD); however, the underlying molecular mechanisms remain unclear. Herein, we used a unique brain-mimetic open system that continuously flows Aβ42 solution to analyze the initial aggregation and adsorptive nature of Aβ42 at physiological concentrations on the lipid membrane. The open system accelerated the adsorption and dimerization kinetics. Upon the addition of Aβ42, monomeric Aβ42 was dominant on the lipid bilayer surface in the closed system with no flow, whereas dimers and high-order oligomers were dominant in the open system. Closed and open systems exhibited different oligomerization kinetics, lipid-Aβ42 interactions, and diffusive properties of monomers and oligomers. These results indicate the specific adsorptive and diffusive nature of Aβ42 on the cell membrane. The open system may help in elucidating the molecular mechanisms underlying AD progression.
淀粉样β 42(Aβ42)肽在脑细胞表面的聚集和积累与阿尔茨海默病(AD)相关;然而,其潜在的分子机制仍不清楚。在此,我们使用了一种独特的模拟大脑的开放系统,该系统持续流动Aβ42溶液,以分析生理浓度下Aβ42在脂质膜上的初始聚集和吸附特性。该开放系统加速了吸附和二聚化动力学。加入Aβ42后,在无流动的封闭系统中,单体Aβ42在脂质双层表面占主导地位,而在开放系统中,二聚体和高阶寡聚体占主导地位。封闭和开放系统表现出不同的寡聚化动力学、脂质 - Aβ42相互作用以及单体和寡聚体的扩散特性。这些结果表明Aβ42在细胞膜上具有特定的吸附和扩散特性。该开放系统可能有助于阐明AD进展的潜在分子机制。