Alzheimer disease (AD) is the most common cause of dementia, characterized by a progressive decline in cognitive function due to the abnormal aggregation and deposition of Amyloid beta (Aβ) fibrils in the brain of patients. In this context, the molecular mechanisms of protein misfolding and aggregation that are known to induce significant biophysical alterations in cells, including destabilization of plasma membranes, remain partially unclear. Physical interaction between the Aβ assemblies and the membrane leads to the disruption of the cell membrane in multiple ways including, surface carpeting, generation of transmembrane channels and detergent-like membrane dissolution. Understanding the impact of amyloidogenic protein in different stages of aggregation with the plasma membrane, plays a crucial role to fully elucidate the pathological mechanisms of AD. Within this framework, computer simulations represent a powerful tool able to shed lights on the interactions governing the structural influence of Aβ proteins on biological membrane. In this study, molecular dynamics (MD) simulations have been performed in order to characterize how POPC bilayer conformational and mechanical properties are affected by the interaction with Aβ_11-42 peptide, oligomer and fibril.

阿尔茨海默氏病（AD）是痴呆症的最常见原因，其特征是由于患者大脑中淀粉样β（Aβ）纤维的异常聚集和沉积，导致认知功能逐渐下降。在这种情况下，蛋白质的错误折叠和聚集的分子机制尚不完全清楚，该分子机制已知会导致细胞发生重大的生物物理变化，包括质膜失稳。Aβ组件与膜之间的物理相互作用以多种方式导致细胞膜破裂，包括表面覆盖，跨膜通道的产生和类似洗涤剂的膜溶解。了解淀粉样蛋白在质膜聚集的不同阶段的影响，在充分阐明AD的病理机制中起着至关重要的作用。在此框架内，计算机模拟代表了一种强大的工具，能够阐明控制Aβ蛋白对生物膜结构影响的相互作用。在这项研究中，进行了分子动力学（MD）模拟，以表征POPC双层构象和机械性能如何受到与Aβ相互作用的影响_11-42肽，低聚物和原纤维。