Guizhou Provincial Key Laboratory of Computational Nano-Material Science, Guizhou Synergetic Innovation Center of Scientific Big Data for Advanced Manufacturing Technology , Guizhou Education University , No. 115, Gaoxin Road , Guiyang , Guizhou 550018 , P. R. China.
School of Information , Guizhou University of Finance and Economics , University City of Huaxi District, Guiyang , Guizhou 550025 , P. R. China.
Langmuir. 2019 Aug 27;35(34):11232-11241. doi: 10.1021/acs.langmuir.9b01802. Epub 2019 Aug 13.
A variety of experimental and theoretical approaches have been employed to investigate the sterol flip-flop motion in lipid bilayer membranes. However, the sterol effect on the dipole potential of lipid bilayer membranes is less well studied and the influence of dipole potential on sterol flip-flop motion in lipid bilayer membranes is less well understood. In our previous works, we have demonstrated the performance of our coarse-grained (CG) model in the computation of the dipole potential. In this work, five 30 μs CG simulations of dimyristoylphosphatidylcholine (DMPC) bilayers were carried out at different sterol concentrations (in a range from 10 to 50% mole fraction). Then, a comparison was made between the effects of cholesterol (CHOL) and 6-ketocholestanol (6-KC) on the dipole potential of DMPC lipid bilayers as well as the sterol flip-flop motion. Our CG simulations show that the membrane dipole potential is impacted more significantly by 6-KC than by CHOL. This finding is consistent with recent experimental studies. Meanwhile, our work suggests that the sterol-sterol interactions (in particular, electrostatic interactions) should be critical to the formation of sterol-sterol clusters, which would hinder the sterol flip-flop motion inside the lipid bilayers. This is in support of the recent experimental study on the sterol transportation in lipid bilayer membranes.
已经采用了多种实验和理论方法来研究甾醇在脂质双层膜中的翻转运动。然而，对于脂质双层膜中甾醇对偶极势的影响研究得较少，对于偶极势对脂质双层膜中甾醇翻转运动的影响了解得也较少。在我们之前的工作中，已经证明了我们的粗粒化（CG）模型在计算偶极势方面的性能。在这项工作中，我们进行了五次不同甾醇浓度（摩尔分数范围为 10%至 50%）的二肉豆蔻酰磷脂酰胆碱（DMPC）双层的 30 μs CG 模拟。然后，比较了胆固醇（CHOL）和 6-酮胆固醇（6-KC）对 DMPC 脂质双层偶极势以及甾醇翻转运动的影响。我们的 CG 模拟表明，6-KC 比 CHOL 更显著地影响膜偶极势。这一发现与最近的实验研究一致。同时，我们的工作表明，甾醇-甾醇相互作用（特别是静电相互作用）对于甾醇-甾醇簇的形成至关重要，这将阻碍脂质双层内的甾醇翻转运动。这支持了最近关于脂质双层膜中甾醇运输的实验研究。
