Ion leakage through transient water pores in protein-free lipid membranes driven by transmembrane ionic charge imbalance
Ion leakage through transient water pores in protein-free lipid membranes driven by transmembrane ionic charge imbalance
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DOI：
10.1529/biophysj.106.094797
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发表时间：
2007-03-15
影响因子：
3.4
通讯作者：
Vattulainen, Ilpo
中科院分区：
文献类型：
--
作者：
Gurtovenko, Andrey A.;Vattulainen, Ilpo
我们利用原子尺度的分子动力学模拟来解决无蛋白磷脂膜中瞬间水孔的离子泄漏问题。我们对含有氯化钠和氯化钾的水溶液中磷脂膜的结果表明，跨膜离子电荷不平衡是活细胞的固有特征，它可以诱导和驱动瞬时水孔的形成和随之而来的离子泄漏。如果梯度足够大，足以产生足够的信号，这些过程就会发生。跨膜的铁路超高电势差。然后可以看到阳离子和阴离子通过水孔的传输；它释放跨膜电位，显著减小水孔的大小，使水孔变得亚稳定，最终导致水孔的密封。研究发现，离子输运对离子类型很敏感。结果表明，尽管Na+离子通过膜的渗透势垒较低，但Na+和Cl-离子通过膜的渗漏比例大致相同。这是因为钠离子与磷脂膜的羰基区域以及形成孔壁的脂头基团有很强的相互作用，从而大大减缓了钠离子的渗透。相反，我们观察到，与氯离子相比，磷脂膜对钾离子的渗透具有明显的选择性：钾离子比钠离子大，只与磷脂头基作用很弱，因此这些相互作用不能弥补K+和Cl-离子渗透的自由能障碍的巨大差异。这些发现被发现对离子的力场参数的选择(由Gromacs和Charmm的离子力场测试)是稳健的。更重要的是，人们发现钾离子能够沿着另一种“水缺陷介导的”途径渗透到膜上，而不会真正形成孔洞。“水缺陷介导的”渗漏只涉及单个水缺陷的形成，并且被发现至少比孔洞介导的离子渗漏快一个数量级。
We have employed atomic-scale molecular dynamics simulations to address ion leakage through transient water pores in protein-free phospholipid membranes. Our results for phospholipid membranes in aqueous solution with NaCl and KCl salts show that the formation of transient water pores and the consequent ion leakage can be induced and be driven by a transmembrane ionic charge imbalance, an inherent feature in living cells. These processes take place if the gradient is large enough to develop a sufficiently signi. cant potential difference across the membrane. The transport of cations and anions through the water pores is then seen; it discharges the transmembrane potential, considerably reduces the size of a water pore, and makes the water pore metastable, leading eventually to its sealing. The ion transport is found to be sensitive to the type of ions. It turns out that Na+ and Cl- ions leak through a membrane at approximately the same ratio despite the fact that Na+ ions are expected to experience a lower potential barrier for the permeation through the pore. This is because of strong interactions of sodium ions with the carbonyl region of a phospholipid membrane as well as with lipid headgroups forming pore "walls,'' considerably slowing down the permeation of sodium ions. In contrast, we observed a pronounced selectivity of a phospholipid membrane to the permeation of potassium ions as compared to chloride ions: Potassium ions, being larger than sodium ions, interact only weakly with phospholipid headgroups, so that these interactions are not able to compensate for a large difference in free-energy barriers for permeation of K+ and Cl- ions. These findings are found to be robust to a choice of force-field parameters for ions (tested by Gromacs and Charmm force-fields for ions). What is more, a potassium ion is found to be able to permeate a membrane along an alternate, "water-defect-mediated'' pathway without actual formation of a pore. The "water-defect-mediated'' leakage involves formation of a single water defect only and is found to be at least one order of magnitude faster than the pore-mediated ion leakage.