Department of Chemical and Biomolecular Engineering University of Akron, Akron, Ohio 44325, USA.
Langmuir. 2010 Mar 2;26(5):3308-16. doi: 10.1021/la903070y.
The adsorption and aggregation of the amyloid-beta (Abeta) peptides on the cell membrane plays a causal role in the pathogenesis of Alzheimer's disease. Here, we report all-atom molecular dynamics (MD) simulations to study the interactions of Abeta oligomer with self-assembled monolayers (SAMs) terminated with hydrophobic CH(3) and hydrophilic OH functional groups, with particular interests in how surface chemistry and Abeta orientation affect the adsorption behavior of Abeta. Simulation results show that the CH(3)-SAM has a stronger binding affinity to Abeta than the OH-SAM does, although both surfaces can induce Abeta adsorption. Regardless of the characteristics of the surface, the hydrophobic C-terminal region is more likely to be adsorbed on the SAMs, indicating a preferential orientation and interface for Abeta adsorption. Structural and energetic comparison among six Abeta-SAM systems further reveals that Abeta orientation, SAM surface hydrophobicity, and interfacial waters all determine Abeta adsorption behavior on the surface, highlighting the importance of hydrophobic interactions at the interface. This work may provide parallel insights into the interactions of Abeta with lipid bilayers.
淀粉样蛋白-β（Abeta）肽在细胞膜上的吸附和聚集在阿尔茨海默病的发病机制中起因果作用。在这里，我们报告了全原子分子动力学（MD）模拟，以研究 Abeta 低聚物与疏水 CH（3）和亲水 OH 官能团终止的自组装单层（SAM）之间的相互作用，特别关注表面化学和 Abeta 取向如何影响 Abeta 的吸附行为。模拟结果表明，尽管两种表面都能诱导 Abeta 吸附，但 CH（3）-SAM 与 Abeta 的结合亲和力比 OH-SAM 更强。无论表面的特点如何，疏水性 C 末端区域更有可能被吸附在 SAM 上，表明 Abeta 吸附的优先取向和界面。六个 Abeta-SAM 系统的结构和能量比较进一步揭示了 Abeta 取向、SAM 表面疏水性和界面水都决定了 Abeta 在表面上的吸附行为，突出了界面处疏水相互作用的重要性。这项工作可以为 Abeta 与脂质双层的相互作用提供平行的见解。
