We show, via molecular simulations, that not only does cholesterol induce a lipid order, but the lipid order also enhances cholesterol localization within the lipid leaflets. Therefore, there is a strong interdependence between these two phenomena. In the ordered phase, cholesterol molecules are predominantly present in the bilayer leaflets and orient themselves parallel to the bilayer normal. In the disordered phase, cholesterol molecules are mainly present near the center of the bilayer at the midplane region and are oriented orthogonal to the bilayer normal. At the melting temperature of the lipid bilayers, cholesterol concentration in the leaflets and the bilayer midplane is equal. This result suggests that the localization of cholesterol in the lipid bilayers is mainly dictated by the degree of ordering of the lipid bilayer. We validate our findings on 18 different lipid bilayer systems, obtained from three different phospholipid bilayers with varying concentrations of cholesterol. To cover a large temperature range in simulations, we employ the Dry Martini force field. We demonstrate that the Dry and the Wet Martini (with polarizable water) force fields produce comparable results.

中文翻译：

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脂质双层中胆固醇分布和构象顺序的相互依赖性。

我们通过分子模拟表明，胆固醇不仅会诱导脂质顺序，而且脂质顺序还会增强胆固醇在脂质小叶中的定位。因此，这两种现象之间存在很强的相互依存关系。在有序相中，胆固醇分子主要存在于双层小叶中，并且自身平行于双层正常。在无序相中，胆固醇分子主要存在于中平面区域的双层中心附近，并且与双层法线正交。在脂质双层的熔化温度下，小叶和双层中平面中的胆固醇浓度相等。该结果表明胆固醇在脂质双层中的定位主要由脂质双层的有序程度决定。我们在 18 种不同的脂质双层系统上验证了我们的发现，这些脂质双层系统是从具有不同胆固醇浓度的三种不同磷脂双层中获得的。为了在模拟中覆盖较大的温度范围，我们采用 Dry Martini 力场。我们证明了干马提尼和湿马提尼（带有可极化水）力场产生的结果相当。