Department of Physics, Texas Tech University, Lubbock, Texas 79409, USA.
J Phys Chem B. 2010 Jun 10;114(22):7516-23. doi: 10.1021/jp101415g.
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 (x(c)) in DOPC bilayers (i.e., from x(c) = 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, with respect to the bilayer normal, both show monotonic decreases as x(c) increases, the average bilayer height shows a significant decrease for x(c) > 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 x(c) 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.
通过原子分子动力学（MD）模拟系统地研究了胆固醇在二油酰基磷脂酰胆碱（DOPC）脂质双层中的凝聚效应。在 323 K 下进行了 14 次独立的 200 ns 模拟，涵盖了 DOPC 双层中胆固醇摩尔分数（x(c)）的整个范围（即 x(c) = 0 至 0.66）。使用基于原子 VDW 半径的切片方法分析了距双层中心不同距离处 DOPC 和胆固醇的分子面积。奇怪的是，虽然每个脂质的平均面积和胆固醇相对于双层法线的倾斜角都随着 x(c)的增加而单调减小，但平均双层高度在 x(c) > 0.35 后会出现显著下降，随后会出现初始增加。脂质的计算部分特定面积清楚地显示了胆固醇的凝聚效应。VDW 面积分析表明，凝聚效应仅限于胆固醇甾体环区域，DOPC 的酰基链在该区域被胆固醇严重压缩。随着 x(c)的增加，DOPC 的头基逐渐沿双层-水界面扩展，以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得到的 DOPC 每单位面积和胆固醇每单位面积的结果不一致：两者都增加，而总的脂质每单位面积却减小。这种不一致源于胆固醇和 DOPC 具有圆柱形形状和相同高度的有问题的假设。我们的结果表明，PC/胆固醇双层的总面积主要由胆固醇甾体环区域的分子堆积决定。提出了一种新的分析方法，该方法考虑了胆固醇的倾斜角和胆固醇甾体环的实际不可压缩性。新的计算表明，由于胆固醇的凝聚效应而损失的大部分面积是从 PC 分子中获得的。
