Department of Computational Biophysics and Bioinformatics, WBBiB, Jagiellonian University, Gronostajowa 7, 30-387 Krakow, Poland.
Department of Bioinformatics, MCB, Jagiellonian University, Gronostajowa 7A, 30-387 Krakow, Poland.
Biochim Biophys Acta Biomembr. 2018 Feb;1860(2):434-441. doi: 10.1016/j.bbamem.2017.10.020. Epub 2017 Oct 25.
In the eye lens, the oxygen partial pressure is very low and the cholesterol (Chol) content in cell membranes is very high. Disturbance of these quantities results in cataract development. In human lens membranes, both bulk phospholipid-Chol domains and the pure Chol bilayer domains (CBDs) were experimentally detected. It is hypothesized that the CBD constitutes a significant barrier to oxygen transport into the lens. Transmembrane profiles of the oxygen diffusion-concentration product, obtained with electron paramagnetic resonance spin-labeling methods, allow evaluation of the oxygen permeability (P) of phospholipid membranes but not the CBD. Molecular dynamics simulation can independently provide components of the product across any bilayer domain, thus allowing evaluation of the P across the CBD. Therefore, to test the hypothesis, MD simulation was used. Three bilayers containing palmitoyl-oleoyl-phosphorylcholine (POPC) and Chol were built. The pure Chol bilayer modeled the CBD, the 1:1 POPC-Chol bilayer modeled the bulk membrane in which the CBD is embedded, and the POPC bilayer was a reference. To each model, 200 oxygen molecules were added. After equilibration, the oxygen concentration and diffusion profiles were calculated for each model and multiplied by each other. From the respective product profiles, the P of each bilayer was calculated. Favorable comparison with experimental data available only for the POPC and POPC-Chol bilayers validated these bilayer models and allowed the conclusion that oxygen permeation across the CBD is ~10 smaller than across the bulk membrane, supporting the hypothesis that the CBD is a barrier to oxygen transport into the eye lens.
在眼睛的晶状体中，氧分压非常低，细胞膜中的胆固醇（Chol）含量非常高。这些数量的干扰会导致白内障的发展。在人眼晶状体膜中，大块磷脂酰胆碱 - 胆固醇域和纯胆固醇双层域（CBD）都被实验检测到。据推测，CBD 构成了氧气进入晶状体的重要障碍。用电子顺磁共振自旋标记方法获得的氧气扩散 - 浓度产物的跨膜分布，可以评估磷脂膜的氧气渗透性（P），但不能评估 CBD。分子动力学模拟可以独立提供任何双层域的产物的组成部分，从而可以评估 CBD 对面的 P。因此，为了验证假设，使用了 MD 模拟。构建了三个含有棕榈酰 - 油酰 - 磷酸胆碱（POPC）和 Chol 的双层。纯 Chol 双层模拟了 CBD，1：1 POPC-Chol 双层模拟了嵌入 CBD 的大块膜，而 POPC 双层则是参考。向每个模型中添加了 200 个氧气分子。达到平衡后，计算了每个模型的氧气浓度和扩散分布，并将它们相乘。从各自的产物分布中，计算了每个双层的 P。与仅适用于 POPC 和 POPC-Chol 双层的实验数据的有利比较验证了这些双层模型，并得出结论，氧气透过 CBD 的渗透率比透过大块膜低约 10 倍，支持了 CBD 是氧气进入眼睛晶状体的障碍的假设。
