Department of Applied Physics and Science Education, Technical University of Eindhoven, PO Box 513, Eindhoven, 5600 MB, The Netherlands.
Institute for Complex Molecular Systems, PO Box 513, Eindhoven, 5600 MB, The Netherlands.
Phys Chem Chem Phys. 2023 Jul 12;25(27):18310-18321. doi: 10.1039/d3cp01692g.
Phospholipids with unsaturated acyl chains are major targets of reactive oxygen species leading to formation of oxidized lipids. Oxidized phospholipids have a pronounced role in cell membrane damage. We investigated the effect of oxidation on physiological properties of phospholipid bilayers using atomistic molecular dynamics simulations. We studied phospholipid bilayer systems of 1-palmitoyl-2-oleoyl--3-phosphocholine (POPC) and its two stable oxidized products, 1-palmitoyl-2-(9'-oxo-nonanoyl)--3-phosphocholine (PoxnoPC) and 1-palmitoyl-2-azelaoyl--3-phosphocholine (PazePC). Structural properties of the POPC lipid bilayer upon the addition of PoxnoPC or PazePC with concentration ranging from 10% to 30% were described. The key finding is that PazePC lipids bend their polar tails toward the bilayer-water interface whereas PoxnoPC lipids orient their tail toward the bilayer interior. The bilayer thickness decreases such that the thickness reduction in bilayers containing PazePC is stronger than in bilayers containing PoxnoPC. The average area per lipid decreases with a stronger effect in bilayers containing PoxnoPC. The addition of PoxnoPC makes both POPC acyl chains slightly more ordered whereas the addition of PazePC reduces the order in the two POPC acyl chains. These structural changes lead to an enhancement in the permeabilities of the bilayers containing these two oxidized products depending on the type, and the amount of oxidation. This enhancement can be achieved with a lower concentration of PazePC (10% or 15%), whereas a higher concentration of PoxnoPC (20%) is required to achieve an apparent enhancement in permeability. While the permeability of bilayers containing PazePC is higher than bilayers containing PoxnoPC in the 10-20% concentration range, by increasing the concentration of the oxidized products to higher than 20%, permeability of the bilayers containing PazePC is reduced such that it is slightly smaller than those containing PoxnoPC.
具有不饱和酰基链的磷脂是活性氧物质的主要靶标，导致氧化脂质的形成。氧化磷脂在细胞膜损伤中起重要作用。我们使用原子分子动力学模拟研究了氧化对磷脂双层生理性质的影响。我们研究了 1-棕榈酰-2-油酰基--3-磷酸胆碱（POPC）及其两种稳定氧化产物 1-棕榈酰-2-（9'-氧代壬酰基）--3-磷酸胆碱（PoxnoPC）和 1-棕榈酰-2-丙二酰基--3-磷酸胆碱（PazePC）的磷脂双层系统。描述了添加浓度为 10%至 30%的 PoxnoPC 或 PazePC 后 POPC 脂质双层的结构特性。主要发现是，PazePC 脂质将其极性尾部弯曲到双层-水界面，而 PoxnoPC 脂质将其尾部朝向双层内部。双层厚度减小，使得含有 PazePC 的双层的厚度减小比含有 PoxnoPC 的双层更强。每个脂质的平均面积减小，在含有 PoxnoPC 的双层中影响更强。添加 PoxnoPC 使两种 POPC 酰基链稍微更有序，而添加 PazePC 降低了两条 POPC 酰基链的有序性。这些结构变化导致含有这两种氧化产物的双层的渗透性增强，具体取决于氧化产物的类型和数量。这种增强可以通过较低浓度的 PazePC（10%或 15%）实现，而需要较高浓度的 PoxnoPC（20%）才能实现渗透性的明显增强。虽然含有 PazePC 的双层的渗透性高于含有 PoxnoPC 的双层在 10-20%浓度范围内，但通过将氧化产物的浓度增加到高于 20%，含有 PazePC 的双层的渗透性降低，使其略小于含有 PoxnoPC 的双层。
