A molecular view of the cholesterol condensing effect in DOPC lipid bilayers.
A molecular view of the cholesterol condensing effect in DOPC lipid bilayers.
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DOI：
10.1021/jp101415g
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发表时间：
2010-06-10
影响因子：
3.3
通讯作者：
Huang, Juyang
中科院分区：
文献类型：
--
作者：
Alwarawrah, Mohammad;Dai, Jian;Huang, Juyang
采用原子分子动力学（MD）模拟方法系统研究了胆固醇在二油酰磷脂酰胆碱（DOPC）脂质双层中的凝聚效应。在323 K下进行了14个独立的200 ns模拟，跨越DOPC双层中胆固醇摩尔分数（xc）的整个范围（即从xc = 0到0.66）。采用基于原子VDW半径的切片方法分析了DOPC和胆固醇在离双层中心不同距离处所占据的分子面积。奇怪的是，虽然每个脂质的平均面积和胆固醇倾斜角相对于双层法线都显示出随着xc增加而单调降低，但平均双层高度在初始增加之后显示出xc > 0.35的显著降低。计算的脂质的部分比面积清楚地显示了胆固醇的凝聚作用。VDW面积分析表明，缩合作用仅限于胆固醇甾醇环区域，其中DOPC的酰基链被胆固醇严重压缩。随着xc的增加，DOPC的头基逐渐沿双层-水界面沿着扩展，占据更多的横向面积。因此，它证实了伞模型的一个关键预测。在高胆固醇摩尔分数下，使用一些现有方法计算的每个DOPC的面积和每个胆固醇的面积显示出不一致的结果：两者都增加，而每个脂质的总面积减少。这种不一致性源于胆固醇和DOPC具有圆柱形形状和相同高度的有问题的假设。我们的研究结果表明，PC/胆固醇双层的总面积主要由胆固醇甾醇环区域的分子堆积决定。提出了一种替代的分析，该区域内的每个分子的面积，其中考虑到胆固醇的倾斜角和胆固醇甾醇环的实际不可压缩性。新的计算表明，由于胆固醇凝聚效应而损失的大部分面积来自PC分子。
The condensing effect of cholesterol in dioleoylphosphatidylcholine (DOPC) lipid bilayers was systematically investigated via atomistic molecular dynamics (MD) simulation. Fourteen independent 200 ns simulations, spanning the entire range of cholesterol mole fraction (xc) in DOPC bilayers (i.e. from xc = 0 to 0.66), were performed at 323 K. The molecular areas occupied by DOPC and cholesterol at different distances from the bilayer center were analyzed using a slicing method based on the VDW radii of atoms. Curiously, while the average area per lipid and the cholesterol tilt angle, in respect to the bilayer normal, both show monotonic decreases as xc increases, the average bilayer height shows a significant decrease for xc > 0.35, following an initial increase. The calculated partial-specific areas of lipids clearly show the condensing effect of cholesterol. The VDW areal analysis showed that the condensing effect is limited only to the cholesterol sterol ring region, where the acyl chains of DOPC are severely compressed by cholesterol. As xc increases, the headgroups of DOPC gradually expand along the bilayer-aqueous interface to occupy more lateral area. Thus, it confirmed a key prediction of the Umbrella model. At high cholesterol mole fractions, the calculated area per DOPC and area per cholesterol using some existing methods showed an inconsistent result: Both increase, while the overall area per lipid decreases. The inconsistency stems from the problematic assumption that cholesterol and DOPC have cylindrical shape and the same height. Our results showed that the total area of a PC/cholesterol bilayer is primarily determined by the molecular packing in the cholesterol sterol ring region. An alternative analysis of area per molecule within this region is proposed, which takes into account the cholesterol tilt angle and the practical incompressibility of cholesterol sterol rings. The new calculation shows that the majority of the area lost due to the cholesterol condensing effect is taken from PC molecules.
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