Transition and Formation of Transmembrane Pore in Stretched Phospholipid Bilayer Including Cholesterol: Molecular Dynamics Simulation
Transition and Formation of Transmembrane Pore in Stretched Phospholipid Bilayer Including Cholesterol: Molecular Dynamics Simulation
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包含胆固醇的拉伸磷脂双层中跨膜孔的转变和形成：分子动力学模拟
DOI：
10.1016/j.bpj.2014.11.471
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Shigeo Wada
中科院分区：
文献类型：
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作者：
Taiki Shigematsu;Kenichiro Koshiyama;Shigeo Wada
我们对拉伸的磷脂/胆固醇双分子层进行分子动力学（MD）模拟，以了解在机械应力下胆固醇对双分子层孔隙形成动力学的影响。通过施加不同的面积应变ε A（由拉伸的双分子层面积与未拉伸的双分子层面积的增加比来定义），用恒定的NPzAT MD模拟拉伸的DPPC/胆固醇双分子层，包括40 mol%的液体有序（L O）相胆固醇，直到形成孔（ε A ~ 1.4）。从MD模拟获得的快照的目视检查中，我们发现孔隙形成的动力学可以分为四个阶段。在第一阶段（0.0≤ε A≤0.3），DPPC分子单调无序。在第二阶段（0.3< ε A≤1.0），两层DPPC分子开始在部分双分子层中交叉，DPPC分子的顺序略有恢复。这表明，L - O相转变为L - O相和互指凝胶（L β I）样相共存。L β I-like相区域随着ε A的增大而增大，并在此阶段的上限附近占主导地位。在第三阶段（1.0< ε A≤1.2），L β i样相双分子层中的DPPC分子再次无序，在第四阶段（1.2< ε A≤1.4），形成跨膜孔。DPPC/胆固醇双分子层孔隙形成的临界面应变（~ 1.4）大约是之前报道的纯DPPC双分子层的两倍，与相应的实验数据在定性上一致。我们怀疑从L O到L β i样相的相变参与了DPPC/胆固醇双分子层在机械应力下的韧性。
We perform molecular dynamics (MD) simulations of stretched phospholipid/cholesterol bilayers to understand effects of cholesterol on the dynamics of pore formation in the bilayer under mechanical stresses. The stretched DPPC/cholesterol bilayers including 40 mol% cholesterol from the liquid-ordered (L O) phase are simulated with constant NPzAT MD simulations by applying various areal strains ε A, defined by the increase ratio of the area of the stretched bilayer to the un-stretched bilayer, until a pore forms (ε A∼ 1.4). From the visual inspection of snapshots obtained by MD simulations, we found the dynamics of the pore formation can be divided into four stages. In the first stage (0.0≤ ε A≤ 0.3), DPPC molecules become disordered monotonically. In the second stage (0.3< ε A≤ 1.0), DPPC molecules of the two monolayers start to interdigitate in a part of the bilayer and the order of DPPC molecules are recovered slightly. This indicates the L O phase transforms to the coexisting phase of L O and an interdigitated gel (L β I) like phases. The region of the L β I-like phase grows with the increase of ε A and dominates near the upper limit of this stage. In the third stage (1.0< ε A≤ 1.2), DPPC molecules in the L β I-like phase bilayer become disordered again, and in the fourth stage (1.2< ε A≤ 1.4), a transmembrane pore forms. The critical areal strain (∼ 1.4), where the pore forms, for the DPPC/cholesterol bilayer is about double of that reported for the pure DPPC bilayer previously, in qualitative agreement with corresponding experimental data. We suspect the phase transition from L O to L β I-like phase is involved into the toughness of the DPPC/cholesterol bilayer under mechanical stresses.