Jørgensen K, Ipsen J H, Mouritsen O G, Bennett D, Zuckermann M J
Royal Danish School of Pharmacy, Copenhagen.
Biochim Biophys Acta. 1991 Feb 25;1062(2):227-38. doi: 10.1016/0005-2736(91)90397-q.
A general microscopic interaction model is proposed to describe the changes in the physical properties of phospholipid bilayer membranes due to foreign molecules which, to different degrees, partition between the membrane phases and the aqueous environment. The model is a multi-state lattice model for the main phase transition of lipid bilayers and the foreign molecules are assumed to intercalate as interstitials in the lattice. By varying the model parameters, the diversity in the thermodynamic properties of the model is explored using computer-simulation techniques which faithfully take account of the thermal fluctuations. The calculations are performed in both the canonical and the grand canonical ensembles corresponding to the cases where the concentration of foreign molecules in the membrane is either fixed or varies as the external conditions are changed. A classification of the diverse thermal behaviour, specifically with regard to the phase diagram, the specific heat, the density fluctuations, and the partition coefficient, is suggested with a view to rationalizing a large body of experimental measurements of the effects of different foreign molecules on membrane properties. The range of foreign molecules considered includes compounds as diverse as volatile general anaesthetics like halothane, cocaine-derived local anaesthetics like procaine, calcium-channel blocking drugs like verapamil, antidepressants like chlorpromazine, and anti-cancer agents like adriamycin.
提出了一种通用的微观相互作用模型，以描述磷脂双层膜物理性质的变化，这些变化是由不同程度地在膜相和水环境之间分配的外来分子引起的。该模型是用于脂质双层主相变的多状态晶格模型，假设外来分子以间隙原子的形式插入晶格中。通过改变模型参数，利用能如实考虑热涨落的计算机模拟技术，探索模型热力学性质的多样性。计算在正则系综和巨正则系综中进行，分别对应膜中外来分子浓度固定或随外部条件变化的情况。针对不同的热行为，特别是关于相图、比热、密度涨落和分配系数，提出了一种分类方法，旨在使大量关于不同外来分子对膜性质影响的实验测量结果合理化。所考虑的外来分子范围包括各种化合物，如氟烷等挥发性全身麻醉剂、普鲁卡因等可卡因衍生的局部麻醉剂、维拉帕米等钙通道阻滞剂、氯丙嗪等抗抑郁药以及阿霉素等抗癌剂。
