Department of Physics, Kasetsart University, Bangkok, Thailand; Computational Biomodelling Laboratory for Agricultural Science and Technology, Faculty of Science, Kasetsart University, Bangkok, Thailand.
Computational Biomodelling Laboratory for Agricultural Science and Technology, Faculty of Science, Kasetsart University, Bangkok, Thailand; Thailand Center of Excellence in Physics, Ministry of Higher Education, Science, Research and Innovation, Bangkok, Thailand; NSTDA Supercomputer Center, National Electronics and Computer Technology Center, National Science and Technology Development Agency, Khlong Luang, Pathumthani, Thailand.
Biophys J. 2021 Oct 19;120(20):4525-4535. doi: 10.1016/j.bpj.2021.08.036. Epub 2021 Sep 1.
We performed a series of molecular dynamics simulations of cholesterol (Chol) in nonoxidized 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphatidylcholine (PLPC) bilayer and in binary mixtures of PLPC-oxidized-lipid-bilayers with 0-50% Chol concentration and oxidized lipids with hydroperoxide and aldehyde oxidized functional groups. From the 60 unbiased molecular dynamics simulations (total of 161 μs), we found that Chol inhibited pore formation in the aldehyde-containing oxidized lipid bilayers at concentrations greater than 11%. For both pure PLPC bilayer and bilayers with hydroperoxide lipids, no pores were observed at any Chol concentration. Furthermore, increasing cholesterol concentration led to a change of phase state from the liquid-disordered to the liquid-ordered phase. This condensing effect of Chol was observed in all systems. Data analysis shows that the addition of Chol results in an increase in bilayer thickness. Interestingly, we observed Chol flip-flop only in the aldehyde-containing lipid bilayer but neither in the PLPC nor the hydroperoxide bilayers. Umbrella-sampling simulations were performed to calculate the translocation free energies and the Chol flip-flop rates. The results show that Chol's flip-flop rate depends on the lipid bilayer type, and the highest rate are found in aldehyde bilayers. As the main finding, we shown that Chol stabilizes the oxidized lipid bilayer by confining the distribution of the oxidized functional groups.
我们对非氧化的 1-棕榈酰-2-亚油酰-sn-甘油-3-磷酸胆碱（PLPC）双层膜以及含有 0-50%胆固醇浓度和氧化脂质的 PLPC-氧化脂质双层的二元混合物中的胆固醇（Chol）进行了一系列分子动力学模拟，氧化脂质具有过氧化物和醛氧化官能团。从 60 个无偏分子动力学模拟（总共 161 μs）中，我们发现胆固醇在浓度大于 11%时抑制了含醛氧化脂质双层中的孔形成。对于纯 PLPC 双层膜和含有过氧化物脂质的双层膜，在任何胆固醇浓度下都没有观察到孔。此外，胆固醇浓度的增加导致从无序液体到有序液体的相状态变化。这种胆固醇的浓缩效应在所有系统中都观察到。数据分析表明，胆固醇的加入会导致双层膜厚度的增加。有趣的是，我们只在含有醛的脂质双层中观察到胆固醇的翻转，而在 PLPC 或过氧化物脂质双层中则没有。我们进行了伞形采样模拟以计算易位自由能和胆固醇翻转速率。结果表明，胆固醇的翻转速率取决于脂质双层的类型，在醛双层中速率最高。作为主要发现，我们表明胆固醇通过限制氧化官能团的分布来稳定氧化脂质双层。
