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 1-棕榈酰-2-亚油酰-sn-甘油-3-磷脂酰胆碱 (PLPC) 双层和 0-50 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％胆浓度和具有氢过氧化物和醛氧化官能团的氧化脂质。从 60 个无偏分子动力学模拟（总共 161 μs ）中，我们发现 Chol 在浓度大于 11% 时抑制含醛氧化脂质双层中的孔形成。对于纯 PLPC 双层和具有氢过氧化物脂质的双层，在任何 Chol 浓度下均未观察到孔。此外，胆固醇浓度的增加导致相态从液体无序相变为液体有序相。在所有系统中都观察到了胆汁的这种凝结效应。数据分析表明，添加 Chol 会导致双层厚度增加。有趣的是，我们仅在含醛脂质双层中观察到 Chol 触发器，而在 PLPC 和氢过氧化物双层中均未观察到。进行伞采样模拟来计算易位自由能和 Chol 翻转率。结果表明，Chol 的翻转率取决于脂质双层的类型，其中醛双层的翻转率最高。作为主要发现，我们表明 Chol 通过限制氧化官能团的分布来稳定氧化脂质双层。