Interaction of Ethanol with Biological Membranes: The Formation of Non-bilayer Structures within the Membrane Interior and their Significance
Interaction of Ethanol with Biological Membranes: The Formation of Non-bilayer Structures within the Membrane Interior and their Significance
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DOI：
10.1021/jp808041z
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发表时间：
2009-02-19
影响因子：
3.3
通讯作者：
Anwar, Jamshed
中科院分区：
文献类型：
--
作者：
Gurtovenko, Andrey A.;Anwar, Jamshed
为了更好地了解乙醇如何影响生物膜，我们进行了一系列原子尺度的分子动力学模拟磷脂膜在水溶液中的乙醇，其浓度从2.5到30摩尔%（无脂基础）。在低于阈值的浓度类似于12摩尔%（30.5体积/体积%）乙醇诱导膜的膨胀，伴随着膜厚度的下降以及无序和增强的脂质酰基链的交错。随着乙醇浓度的增加，这些变化变得更加明显，但膜的双层结构得以保持。在阈值浓度以上，脂质-水界面中的多个瞬时缺陷的出现最终导致一些脂质在膜内部解吸和组装成非双层结构。这些结构，是小的和不规则的，类似于倒置胶束，并具有长寿命的字符。此外，非双层结构的形成伴随着属于相对膜小叶的脂质的混合，从而导致膜结构的不可逆变化。值得注意的是，在膜内部的非双层结构的形成，在良好的协议与实验数据的观察，被发现是强大的模拟条件（系统的大小和盐的存在下）和类型的脂质（磷脂酰胆碱和磷脂酰乙醇胺）。我们讨论了这些非双层结构的意义与众所周知的能力，乙醇，以促进膜半融合，以及与可能的作用的胶束状结构作为一个交付系统的极性溶质和离子。乙醇对双层结构的“损伤”也表明，强烈的酒精饮料（类似于40 v/v %）可能对直接接触高浓度乙醇的人体上皮组织（如嘴唇，口腔，喉咙，食道和胃）有潜在危害。
To gain a better understanding of how ethanol affects biological membranes, we have performed a series of atomic-scale molecular dynamics simulations of phospholipid membranes in aqueous solution with ethanol, whose concentration was varied from 2.5 to 30 mol % (lipid-free basis). At concentrations below the threshold value of similar to 12 mol % (30.5 v/v %) ethanol induces expansion of the membrane, accompanied by a drop in the membrane thickness as well as disordering and enhanced interdigitation of lipid acyl chains. These changes become more pronounced with increase in ethanol concentration, but the bilayer structure of the membrane is maintained. Above the threshold concentration the appearance of multiple transient defects in the lipid water interface eventually gives rise to desorption and assembly of some of the lipids into non-bilayer structures within the membrane interior. These structures, being small and irregular, resemble inverted micelles and have a long-lived character. Furthermore, formation of the non-bilayer structures is accompanied by mixing of lipids that belong to the opposite membrane leaflets, thereby leading to irreversible changes in the membrane structure. Remarkably, this observation of the formation of non-bilayer structures within the membrane interior, being in good agreement with experimental data, is found to be robust with respect to both the simulation conditions (the system size and the presence of salt) and the type of lipids (phosphatidylcholine and phosphatidylethanolamine). We discuss the significance of these non-bilayer structures in relation with the well-known ability of ethanol to promote membrane hemifusion as well as with the possible role of the micelle-like structures as a delivery system for polar solutes and ions. The ethanol-induced "damage" to the bilayer structure also suggests that strong alcoholic beverages (similar to 40 v/v %) might be potentially hazardous to the epithelial tissues of the human body (such as lips, mouth, throat, gullet, and stomach) that come in direct contact with high-concentrations of ethanol.