Department of Agricultural and Biological Engineering, Purdue University, West Lafayette, IN 47907, USA.
Phys Chem Chem Phys. 2018 Mar 7;20(10):6817-6829. doi: 10.1039/c7cp07148e.
Some amyloid related proteins/peptides are involved in aggregation and pore formation in phospholipid membranes (cell membranes), which result in a variety of neurological disorders such as Alzheimer's disease, Parkinson's disease and Huntington disease. In this research, the mechanism of pore formation by β amyloid (Aβ) peptides was investigated using molecular dynamics simulation by simulating the interaction of the Aβ(11-42) peptide, with a lipid membrane and the potential of the mean force of interaction was evaluated. A 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membrane system with different cholesterol concentrations was used to simulate the neural cell membrane. The results indicated that Aβ(11-42) peptide oligomers with peptide numbers larger than two were more likely to lead to lipid deformation and water channels, and the free energy of penetration into the membrane decreased with the increasing number of peptides. Increasing the concentration of cholesterol leads to a higher energy barrier for the penetration of peptide into the lipid bilayer thereby protecting the membrane. The results of this research have potential application in the prevention of pore formation by Aβ aggregates on the lipid membrane.
一些淀粉样相关蛋白/肽参与磷脂膜（细胞膜）中的聚集和孔形成，这导致了各种神经紊乱，如阿尔茨海默病、帕金森病和亨廷顿病。在这项研究中，通过分子动力学模拟研究了β淀粉样（Aβ）肽的孔形成机制，模拟了 Aβ（11-42）肽与脂质膜的相互作用，并评估了相互作用的平均势能。使用具有不同胆固醇浓度的 1-棕榈酰基-2-油酰基-sn-甘油-3-磷酸胆碱（POPC）膜系统来模拟神经细胞膜。结果表明，具有两个以上肽数的 Aβ（11-42）肽低聚物更有可能导致脂质变形和水通道，并且进入膜的自由能随着肽数的增加而降低。胆固醇浓度的增加会导致肽进入脂质双层的穿透能垒升高，从而保护膜。这项研究的结果在预防 Aβ 聚集物在脂质膜上形成孔方面具有潜在的应用。
