Predictions of Phase Separation in Three-Component Lipid Membranes by the MARTINI Force Field
Predictions of Phase Separation in Three-Component Lipid Membranes by the MARTINI Force Field
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DOI：
10.1021/jp4000686
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发表时间：
2013-04-18
影响因子：
3.3
通讯作者：
Laradji, Mohamed
中科院分区：
文献类型：
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作者：
Davis, Ryan S.;Kumar, P. B. Sunil;Laradji, Mohamed
通过分子动力学模拟系统地研究了由二棕榈酰磷脂酰胆碱（DPPC）、胆固醇（Chol）和不饱和磷脂酰胆碱（PC）组成的三组分脂质双层的粗粒 MARTINI 模型的相行为。本研究的目的是了解哪些类型的不饱和 PC 在添加到 DPPC 和 Chol 的混合物中时会诱导形成热力学稳定的共存相，并揭示驱动此类三组分混合物中相分离的机制。我们的模拟表明，目前使用的 MARTINI 力场不会在 DPPC、Chol 和低不饱和度水平的不饱和 PC（例如棕榈酰油酰磷脂酰胆碱 (POPC) 或二油酰磷脂酰胆碱 (DOPC)）的混合物中引起这种相分离。此外，我们发现相分离确实发生在 DPPC、Chol 和多不饱和 PC（例如二亚油酰磷脂酰胆碱 (DUPC) 和二花生四烯酰磷脂酰胆碱 (DAPC)）的混合物中。通过系统地调整 PC 分子疏水基团之间的相互作用，我们表明，通过 MARTINI 力场建模，三组分脂质双层中相分离的出现主要是由于粗粒分子（即珠子）之间的相互作用，而不是由于饱和和不饱和脂质酰基链构象之间的差异（即熵驱动）。
The phase behavior of the coarse-grained MARTINI model for three-component lipid bilayers composed of dipalmytoyl-phosphatidylcholine (DPPC), cholesterol (Chol), and an unsaturated phosphatidylcholine (PC) was systematically investigated by molecular dynamics simulations. The aim of this study is to understand which types of unsaturated PC induce the formation of thermodynamically stable coexisting phases when added to mixtures of DPPC and Chol and to unravel the mechanisms that drive phase separation in such three-component mixtures. Our simulations indicate that the currently used MARTINI force field does not induce such phase separation in mixtures of DPPC, Chol, and unsaturated PCs with a low unsaturation level, such as palmitoyl-oleoyl-phosphatidylcholine (POPC) or dioleoyl-phosphatidylcholine (DOPC). Also, we found that phase separation does occur in mixtures of DPPC, Chol, and polyunsaturated PCs, such as dilinoleyl-phosphatidylcholine (DUPC) and diarachidonoyl-phosphatidylcholine (DAPC). Through systematic tweaking of the interactions between the hydrophobic groups of the PC molecules, we show that the appearance of phase separation in three-component lipid bilayers, as modeled through the MARTINI force field, is primarily due to the interactions between the coarse-grained molecules, i.e., the beads, rather than due to the differences between the conformations of saturated and unsaturated lipid acyl chains, namely entropy driven.