A microscopic interaction model of maximum solubility of cholesterol in lipid bilayers
A microscopic interaction model of maximum solubility of cholesterol in lipid bilayers
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DOI：
10.1016/s0006-3495(99)77369-8
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发表时间：
1999-04-01
影响因子：
3.4
通讯作者：
Feigenson, GW
中科院分区：
文献类型：
--
作者：
Huang, JY;Feigenson, GW
我们最近报道了胆固醇在脂双层chi(Chol)*中的平衡最大溶解度为0.66，在四种不同的磷脂酰胆碱中的溶解度为0.51，在磷脂酰乙醇胺中的平衡最大溶解度为0.51(Huang，J.，J.T.Buboltz，和G.W.Feigenson)。1999年。毕奇姆。生物群落。行动。在新闻发布会上)。在这里，我们提出了一个胆固醇-磷脂混合模型，解释了X-CHOL*的这些观测值。蒙特卡罗模拟表明，最近邻相互作用的成对可加性不足以描述所有的chi(Chol)*值。相反，如果胆固醇多体相互作用被分配了非常不利的能量，那么胆固醇化学势就会发生跳跃，导致其从双层中析出。胆固醇沉淀最有可能发生在胆固醇摩尔分数的三个离散值0.50、0.57和0.67附近，这三个值分别对应于1/1、4/3和2/1的胆固醇/磷脂摩尔比。在这些溶解度极限下，当胆固醇化学势跃升时，胆固醇-磷脂双层混合物形成高度规则的脂质分布，以最大限度地减少胆固醇-胆固醇的接触。这种处理表明，在特定的胆固醇摩尔组分上可以发生戏剧性的结构和热力学变化，而不会形成任何化学计量比的络合物。不利的胆固醇多体相互作用的物理起源可以用“保护伞模型”来解释：在双层中，非极性胆固醇依赖于极性磷脂头基的覆盖来避免胆固醇与水接触的不利的自由能。因此，在高胆固醇摩尔分数，这种不利的自由能，而不是任何有利的胆固醇-磷脂相互作用，主导着混合行为。这一物理起源；也解释了“胆固醇缩合效应”和胆固醇-磷脂混合物中酰链有序参数的增加。
We recently reported the equilibrium maximum solubility of cholesterol in a lipid bilayer, chi(chol)*, to be 0.66 in four different phosphatidylcholines, and 0.51 in a phosphatidylethanolamine (Huang, J., J. T. Buboltz, and G. W. Feigenson. 1999. Biochim. Biophys. Acta. in press). Here we present a model of cholesterol-phospholipid mixing that explains these observed values of X-chol*. Monte Carlo simulations show that;pairwise-additivity of nearest-neighbor interactions is inadequate to describe all the chi(chol)* values. Instead, if cholesterol multibody interactions are assigned highly unfavorable energy, then jumps occur in cholesterol chemical potential that lead to its precipitation from the bilayer. Cholesterol precipitation is most likely to occur near three discrete values of cholesterol mole fraction, 0.50, 0.57, and 0.67, which correspond to cholesterol/ phospholipid mole ratios of 1/1, 4/3, and 2/1, respectively. At these solubility limits, where cholesterol chemical potential jumps, the cholesterol-phospholipid bilayer mixture forms highly regular lipid distributions in order to minimize cholesterol-cholesterol contacts. This treatment shows that dramatic structural and thermodynamic changes can occur at particular cholesterol mole fractions without any stoichiometric complex formation. The physical origin of the unfavorable cholesterol multibody interaction is explained by an "umbrella model": in a bilayer, nonpolar cholesterol relies on polar phospholipid headgroup coverage to avoid the unfavorable free energy of cholesterol contact with water. Thus, at high cholesterol mole fraction, this unfavorable free energy, not any favorable cholesterol-phospholipid interaction,dominates the mixing behavior. This physical origin;also explains the "cholesterol condensing effect" and the;increase in acyl chain order parameter in cholesterol-phospholipid mixtures.