Gurtovenko Andrey A, Miettinen Markus, Karttunen Mikko, Vattulainen Ilpo
Laboratory of Physics and Helsinki Institute of Physics, Helsinki University of Technology, P.O. Box 1100, FI-02015 HUT, Finland.
J Phys Chem B. 2005 Nov 10;109(44):21126-34. doi: 10.1021/jp053667m.
An atomic-scale understanding of cationic lipid membranes is required for development of gene delivery agents based on cationic liposomes. To address this problem, we recently performed molecular dynamics (MD) simulations of mixed lipid membranes comprised of cationic dimyristoyltrimethylammonium propane (DMTAP) and zwitterionic dimyristoylphosphatidylcholine (DMPC) (Biophys. J. 2004, 86, 3461-3472). Given that salt ions are always present under physiological conditions, here we focus on the effects of monovalent salt (NaCl) on cationic (DMPC/DMTAP) membranes. Using atomistic MD simulations, we found that salt-induced changes in membranes depend strongly on their composition. When the DMTAP mole fraction is small (around 6%), the addition of monovalent salt leads to a considerable compression of the membrane and to a concurrent enhancement of the ordering of lipid acyl chains. That is accompanied by reorientation of phosphatidylcholine headgroups in the outward normal direction and slight changes in electrostatic properties. We attribute these changes to complexation of DMPC lipids with Na(+) ions which penetrate deep into the membrane and bind to the carbonyl region of the DMPC lipids. In contrast, at medium and high molar fractions of cationic DMTAP (50 and 75%) a substantial positive surface charge density of the membranes prevents the binding of Na(+) ions, making such membranes almost insensitive to monovalent salt. Finally, we compare our results to the Poisson-Boltzmann theory. With the exception of the immediate vicinity of the bilayer plane, we found excellent agreement with the theory. This is as expected since unlike in the theoretical description the surface is now structured due to its atomic scale nature.
基于阳离子脂质体的基因传递剂的开发需要对阳离子脂质膜有原子尺度的理解。为了解决这个问题，我们最近对由阳离子二肉豆蔻酰基三甲基铵丙烷（DMTAP）和两性离子二肉豆蔻酰基磷脂酰胆碱（DMPC）组成的混合脂质膜进行了分子动力学（MD）模拟（《生物物理杂志》，2004年，86卷，3461 - 3472页）。鉴于生理条件下总是存在盐离子，在此我们重点研究单价盐（NaCl）对阳离子（DMPC/DMTAP）膜的影响。通过原子尺度的MD模拟，我们发现盐诱导的膜变化强烈依赖于其组成。当DMTAP摩尔分数较小时（约6%），添加单价盐会导致膜显著压缩，并同时增强脂质酰链的有序性。这伴随着磷脂酰胆碱头部基团向外法线方向的重新定向以及静电性质的轻微变化。我们将这些变化归因于DMPC脂质与深入膜内并与DMPC脂质的羰基区域结合的Na(+)离子的络合。相反，在阳离子DMTAP的中等和高摩尔分数（50%和75%）下，膜的大量正表面电荷密度阻止了Na(+)离子的结合，使得这种膜对单价盐几乎不敏感。最后，我们将我们的结果与泊松 - 玻尔兹曼理论进行比较。除了双层平面的紧邻区域外，我们发现与该理论有很好的一致性。这是预期的，因为与理论描述不同，由于其原子尺度性质，现在表面是有结构的。
