Interactions between amyloid-β peptide (Aβ) and the cell membrane include interaction with membrane lipids and binding to membrane receptors, both of which are considered to be the toxicity mechanisms of Aβ. However, it is unclear whether both mechanisms lead to cytotoxicity. Thus, we aimed to analyze these two mechanisms of Aβ42 interaction with cell membranes under different Aβ aggregation states. To this end, model membrane experiments were conducted. Quantitative analysis of Aβ42 monomers or oligomers bound to the membrane of neuro-2a cells was also performed, and laser confocal microscopy was employed to assess endocytosis of FITC-Aβ42 monomers or oligomers by neuro-2a cells. We found that the binding capacity of Aβ42 to membrane lipids was weak and that the amount of Aβ42 bound to membrane lipids was low. Moreover, clathrin-mediated endocytosis of Aβ42 oligomers by neuro-2a cells was observed. Endocytosis serves as a key mode of interaction between extracellular Aβ42 and neurons. These findings provide insights into the mechanisms underlying Aβ oligomer metabolism.

中文翻译：

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内吞作用是细胞外β-淀粉样蛋白与细胞膜相互作用的关键模式

淀粉样蛋白-β肽（Aβ）与细胞膜的相互作用包括与膜脂的相互作用和与膜受体的结合，这两者被认为是Aβ的毒性机制。然而，尚不清楚这两种机制是否会导致细胞毒性。因此，我们旨在分析 Aβ42 在不同 Aβ 聚集状态下与细胞膜相互作用的这两种机制。为此，进行了模型膜实验。还对与 neuro-2a 细胞膜结合的 Aβ42 单体或寡聚体进行了定量分析，并采用激光共聚焦显微镜评估 neuro-2a 细胞对 FITC-Aβ42 单体或寡聚体的内吞作用。我们发现 Aβ42 与膜脂的结合能力弱，与膜脂结合的 Aβ42 的量很低。而且，观察到网格蛋白介导的神经 2a 细胞对 Aβ42 寡聚体的内吞作用。内吞作用是细胞外 Aβ42 与神经元之间相互作用的关键模式。这些发现提供了对 Aβ 寡聚体代谢潜在机制的见解。