Department of Biology, University of Fribourg, Chemin du Musée 10, 1700 Fribourg, Switzerland.
Soft Matter. 2023 May 10;19(18):3377-3385. doi: 10.1039/d2sm01419j.
Surface pressure-area isotherms of lipid monolayers at the air-water interface provide essential information about the structure and mechanical behaviour of lipid membranes. These curves can be readily obtained through Langmuir trough measurements and, as such, have been collected for decades in the field of membrane biochemistry. However, it is still challenging to directly observe and understand nanoscopic features of monolayers through such experiments, and molecular dynamics (MD) simulations are generally used to provide a molecular view of such interfaces. In MD simulations, the surface pressure-area (-) isotherms are generally computed using the Kirkwood-Irving formula, that relies on the evaluation of the pressure tensor. This approach, however, has intrinsic limitations when the molecular area in the monolayer is low (typically < 60 Å per lipid). Recently, an alternative method to compute - isotherms of surfactants, based on the calculation of the three-dimensional osmotic pressure the implementation of semipermeable barriers was proposed. In this work, we investigate the feasibility of this approach for long-chain surfactants such as phospholipids. We identify some discrepancies between the computed values and experimental results, and we propose a semi-empirical correction based on the molecular structure of the surfactants at the monolayer interface. To validate the potential of this new approach, we simulate several phosphatidylcholine and phosphatidylethanolamine lipids at various temperatures using all-atom and coarse-grained force fields, and we compute the corresponding - isotherms. Our results show that the - isotherms obtained using the new method are in very good agreement with experiments and far superior to the canonical pressure tensor-based method at low molecular areas. This corrected osmotic pressure method allows for accurate characterization of the molecular packing in monolayers in various physical phases.
脂质单层在气-水界面的表面压力-面积等温线提供了关于脂质膜结构和力学行为的基本信息。这些曲线可以通过 Langmuir 槽测量很容易地获得，因此在膜生物化学领域已经收集了几十年。然而，通过这些实验直接观察和理解单层的纳米级特征仍然具有挑战性，通常使用分子动力学 (MD) 模拟来提供这种界面的分子视图。在 MD 模拟中，表面压力-面积 (-) 等温线通常使用 Kirkwood-Irving 公式计算，该公式依赖于压力张量的评估。然而，当单层中的分子面积较低（通常每个脂质 < 60 Å）时，这种方法存在内在限制。最近，提出了一种基于计算三维渗透压的替代方法来计算表面活性剂的 - 等温线，该方法实现了半渗透屏障。在这项工作中，我们研究了这种方法对于长链表面活性剂（如磷脂）的可行性。我们发现计算值和实验结果之间存在一些差异，并提出了一种基于单层界面上表面活性剂分子结构的半经验修正。为了验证这种新方法的潜力，我们使用全原子和粗粒力场模拟了几种磷脂酰胆碱和磷脂酰乙醇胺脂质在不同温度下的情况，并计算了相应的 - 等温线。我们的结果表明，使用新方法获得的 - 等温线与实验非常吻合，并且在低分子面积下远优于基于经典压力张量的方法。这种修正的渗透压方法允许在各种物理相中层中对分子堆积进行准确的特征描述。
