淀粉样多肽Aβ的变性过程可激活一系列病理事件，是阿兹海默症病人脑内神经细胞产生损伤的主要原因。然而，Aβ如何产生错误折叠及纤维化的机制尚未明确，因此极大地影响了阿兹海默症的诊疗及新药研发。本项目拟从细胞膜的手性本征出发，探索生物膜界面的手性如何影响Aβ的折叠及纤维化过程。通过构建具有不同手性的生物膜界面体系，以高速扫描原子力显微镜为主要工具，发展生物膜界面上高分辨微区分析方法，实时原位动态地表征Aβ与手性生物膜界面相互作用全过程，揭示其分子机制。同时，利用不同手性界面诱导产生的Aβ聚集体及纤维，研究其与神经细胞相互作用的差异，在细胞层次上揭示Aβ产生细胞毒性的机制。本工作将提供一个新的视角去理解体内蛋白/多肽淀粉样变性的分子机制，并为神经退行性疾病的药物分子设计提供重要的参考。

The amyloidosis of amyloid peptides Aβ can activate a series of pathological processes, which are the main reasons for the damage of neurons in the brain of Alzheimers’brains. However, the mechanism for the misfolding and fibrillation of Aβ is still unclear, which significantly affect the therapeutics and drug discovery of Alzheimer’s disease. Inspired by the chirality nature of cytomembrane, we propose here to investigate how the chirality of biomembrane interface influences the misfolding and fibrillation of Aβ. We will fabricate a series of biomembrane systems with different chirality, and develop high-resolution microanalysis method for biomembrane interface with the help of high-speed atomic force microscope. We will in-situ characterize the interaction between Aβ and chiral biomembrane interface in real-time, and reveal its molecular mechanism. Meanwhile, we will utilize the aggregates induced by different chiral biomembranes to interact with neurons, and then disclose the origin of cytotoxicity of Aβ. This project will provide new insight for understanding the molecule mechanism of Aβ amyloidosis, and lead to innovation in therapeutics of neurodegenerative diseases.