Molecular dynamics study of the behavior of selected nanoscale building blocks in a gel-phase lipid bilayer.
Molecular dynamics study of the behavior of selected nanoscale building blocks in a gel-phase lipid bilayer.
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凝胶相脂质双层中选定纳米级结构单元行为的分子动力学研究。
DOI：
10.1021/jp1039942
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
McCabe,Clare
中科院分区：
文献类型：
--
作者：
Redmill,PatrickS;McCabe,Clare
细胞膜在细胞内外区域之间起着调节屏障的作用。为了让分子从细胞外液到达细胞内部，它必须通过主动或被动的运输跨膜扩散。作为细胞膜的关键组成部分，脂质双层的刚性结构阻止了大多数颗粒的简单扩散，而重要的营养物质通过特定的机制运输到内部，如离子通道和运输蛋白。尽管细胞膜为细胞提供了保护，使其免受细胞外介质中有害毒素的影响，但一些外来颗粒可以到达细胞内部，导致细胞功能的异常。这种行为对于分子结构紧凑的渗透剂尤其明显，这表明常见的纳米级构建块，如富勒烯，可能会进入细胞内部。为了测量这种粒子穿过膜的倾向，我们使用分子动力学模拟和平均作用力计算，计算了两个纳米构筑块C60和一个氢端多面体低聚硅氧烷(H-POSS)单体在水合二棕榈酰磷脂酰胆碱(DPPC)双层膜中沿垂直于双层表面的轴线的Gibbs自由能。研究表明，C60对双分子膜体系中位于水/双分子膜界面下方的软聚合物区域具有较强的能量优势，其从体水的跃迁能为19.8kcal/−。C60从主体水到双层中心的转变虽然在能量上也是有利的，但必须克服疏水脂尾区域的+5.9kcal/mol能垒。H-POSS模拟表明，在水−双层界面处有一个能量极小值，其能量为−10.9kcal/m ol，但在疏水致密脂肪族区域也观察到了一个局部极小值−2.7kcal/m o l。在C60研究的疏水核心区看到的能量障碍很可能是由于将相对较大的粒子插入如此密集的区域而带来的显著惩罚。相反，尽管H-POSS被发现在插入双层时受到能量惩罚，但H-POSS溶质的相对较小的尺寸使得这种惩罚不那么显著。H-POSS单体在软聚合物区域出现的势垒主要是由于界面区域没有良好的溶质-双分子层静电相互作用，而软聚合物区域的范德华相互作用比稠密脂肪族区域少。这些结果表明，C60可能会分配到DPPC/水体系的有机相中，因为在软聚合物和双层的致密脂肪族区域具有有利的自由能，而H-POSS可能分配在水−双层界面附近，在那里粒子与双层的极性头部基团具有低能量的静电相互作用。
The cellular membrane functions as a regulating barrier between the intracellular and extracellular regions. For a molecule to reach the interior of the cell from the extracellular fluid, it must diffuse across the membrane, via either active or passive transport. The rigid structure of lipid bilayers, which are a key component of cellular membranes, prohibit simple diffusion of most particles, while vital nutrients are transported to the interior by specific mechanisms, such as ion channels and transport proteins. Although the cellular membrane provides the cell with protection against unwanted toxins that may be in the extracellular medium, some foreign particles can reach the interior of the cell, resulting in irregularities in cellular function. This behavior is particularly noted for permeants with compact molecular structure, suggesting that common nanoscale building blocks, such as fullerenes, may enter into the interior of a cell. To gauge the propensity for such particles to cross the membrane, we have computed the Gibbs free energy of transfer along the axis normal to the bilayer surface for two nanoscale building blocks, C60and a hydrogen-terminated polyhedral oligomeric silsequioxane (H-POSS) monomer, in a hydrated dipalmitoylphosphatidylcholine (DPPC) bilayer using molecular dynamics simulations and potential of mean force calculations. The studies show that C60has a substantial energetic preference for the soft polymer region of the lipid bilayer system, below the water/bilayer interface, with a transition energy from bulk water of −19.8 kcal/mol. The transition of C60from the bulk water to the center of the bilayer, while also energetically favorable, has to overcome a +5.9 kcal/mol energetic barrier in the hydrophobic lipid tail region. The H-POSS simulations indicate an energy minimum at the water−bilayer interface, with an energy of −10.9 kcal/mol; however, a local minimum of −2.7 kcal/mol is also observed in the hydrophobic dense aliphatic region. The energy barrier seen in the hydrophobic core region of the C60study is likely due to the significant penalty associated with inserting the relatively large particle into such a dense region. In contrast, whereas H-POSS is found to be subject to an energetic penalty upon insertion into the bilayer, the relatively small size of the H-POSS solute renders this penalty less significant. The energy barrier seen in the soft polymer region for the H-POSS monomer is primarily attributed to the lack of favorable solute-bilayer electrostatic interactions, which are present in the interfacial region, and fewer van der Waals interactions in the soft polymer region than the dense aliphatic region. These results indicate that C60may partition into the organic phase of the DPPC/water system, given the favorable free energies in the soft polymer and dense aliphatic regions of the bilayer, and H-POSS is likely to partition near the water−bilayer interface, where the particle has low-energy electrostatic interactions with the polar head groups of the bilayer.