Khandelia Himanshu, Mouritsen Ole G
MEMPHYS-Center for Biomembrane Physics, Department of Physics and Chemistry, University of Southern Denmark, Campusvej 55, DK-5230 Odense M, Denmark.
Biophys J. 2009 Apr 8;96(7):2734-43. doi: 10.1016/j.bpj.2009.01.007.
In oxidative environments, biomembranes contain oxidized lipids with short, polar acyl chains. Two stable lipid oxidation products are PoxnoPC and PazePC. PoxnoPC has a carbonyl group, and PazePC has an anionic carboxyl group pendant at the end of the short, oxidized acyl chain. We have used MD simulations to explore the possibility of complete chain reversal in OXPLs in POPC-OXPL mixtures. The polar AZ chain of PazePC undergoes chain reversal without compromising the lipid bilayer integrity at concentrations up to 25% OXPL, and the carboxyl group points into the aqueous phase. Counterintuitively, the perturbation of overall membrane structural and dynamic properties is stronger for PoxnoPC than for PazePC. This is because of the overall condensing and ordering effect of sodium ions bound strongly to the lipids in the PazePC simulations. The reorientation of AZ chain is similar for two different lipid force fields. This work provides the first molecular evidence of the "extended lipid conformation" in phospholipid membranes. The chain reversal of PazePC lipids decorates the membrane interface with reactive, negatively charged functional groups. Such chain reversal is likely to exert a profound influence on the structure and dynamics of biological membranes, and on membrane-associated biological processes.
在氧化环境中，生物膜含有具有短极性酰基链的氧化脂质。两种稳定的脂质氧化产物是PoxnoPC和PazePC。PoxnoPC含有一个羰基，而PazePC在短的氧化酰基链末端有一个阴离子羧基侧链。我们使用分子动力学模拟来探究在POPC - OXPL混合物中氧化磷脂（OXPLs）完全链反转的可能性。在OXPL浓度高达25%时，PazePC的极性AZ链发生链反转，且不影响脂质双层的完整性，羧基指向水相。与直觉相反的是，PoxnoPC对整体膜结构和动力学性质的扰动比PazePC更强。这是因为在PazePC模拟中，钠离子与脂质强烈结合产生的整体凝聚和有序效应。对于两种不同的脂质力场，AZ链的重新定向是相似的。这项工作提供了磷脂膜中“扩展脂质构象”的首个分子证据。PazePC脂质的链反转用带负电荷的反应性功能基团修饰膜界面。这种链反转可能会对生物膜的结构和动力学以及与膜相关的生物过程产生深远影响。
