Due to an aging population, neurodegenerative diseases such as Alzheimer’s disease (AD) have become a major health issue. In the case of AD, Aβ_1–42 peptides have been identified as one of the markers of the disease with the formation of senile plaques via their aggregation, and could play a role in memory impairment and other tragic syndromes associated with the disease. Many studies have shown that not only the morphology and structure of Aβ_1–42 peptide assembly are playing an important role in the formation of amyloid plaques, but also the interactions between Aβ_1–42 and the cellular membrane are crucial regarding the aggregation processes and toxicity of the amyloid peptides. Despite the increasing amount of information on AD associated amyloids and their toxicity, the molecular mechanisms involved still remain unclear and require in-depth investigation at the local scale to clearly decipher the role of the sequence of the amyloid peptides, of their secondary structures, of their oligomeric states, and of their interactions with lipid membranes. In this original study, through the use of Atomic Force Microscopy (AFM) related-techniques, high-speed AFM and nanoInfrared AFM, we tried to unravel at the nanoscale the link between aggregation state, structure and interaction with membranes in the amyloid/membrane interaction. Using three mutants of Aβ peptides, L34T, oG37C, and WT Aβ_1–42 peptides, with differences in morphology, structure and assembly process, as well as model lipidic membranes whose composition and structure allow interactions with the peptides, our AFM study coupling high spatial and temporal resolution and nanoscale structure information clearly evidences a local correlation between the secondary structure of the peptides, their fibrillization kinetics and their interactions with model membranes. Membrane disruption is associated to small transient oligomeric entities in the early stages of aggregation that strongly interact with the membrane, and present an antiparallel β-sheet secondary structure. The strong effect on membrane integrity that exists when these oligomeric Aβ_1–42 peptides interact with membranes of a particular composition could be a lead for therapeutic studies.

由于人口老龄化，诸如阿尔茨海默氏病（AD）等神经退行性疾病已成为主要的健康问题。在AD的情况下，Aβ _{1 - 42种}肽已被鉴定为与通过它们的聚集的老年斑形成的疾病的标记物中的一个，并且可以发挥在记忆障碍和与疾病相关的其他悲惨综合征的作用。许多研究表明，不仅形态和Aβ的结构_{1 - 42}肽组装在玩在淀粉样蛋白斑的形成中起重要作用，而且还Aβ间的相互作用_{1 - 42}细胞膜和细胞膜对于淀粉样肽的聚集过程和毒性至关重要。尽管有关AD相关淀粉样蛋白及其毒性的信息越来越多，但所涉及的分子机制仍不清楚，需要在当地进行深入研究，以明确破译淀粉样蛋白肽序列，其二级结构，它们的低聚物状态，以及它们与脂质膜的相互作用。在这项原始研究中，我们通过使用原子力显微镜（AFM）相关技术，高速原子力显微镜（AFM）和纳米红外原子力显微镜（AFM），试图在纳米尺度上揭示淀粉样蛋白/膜中聚集状态，结构以及与膜的相互作用之间的联系。相互作用。使用Aβ肽，L34T，oG37C和WTAβ的三种突变体_{1– 42种}具有不同形态，结构和组装过程的肽，以及组成和结构允许与肽相互作用的脂质膜模型，我们的AFM研究结合了高时空分辨率和纳米级结构信息，清楚地证明了它们之间的局部相关性肽的二级结构，它们的原纤维化动力学及其与模型膜的相互作用。膜破坏与聚集初期与膜强烈相互作用的小瞬态寡聚实体有关，并呈现出反平行的β-sheet二级结构。对膜完整性存在的强烈影响，当这些低聚Aβ _{1 - 42} 肽与特定组成的膜相互作用可能是治疗研究的先导。