Molecular Biophysics, University of Kaiserslautern, Erwin-Schrödinger-Str. 13, 67663 Kaiserslautern, Germany.
Nanoscale. 2015 Dec 28;7(48):20685-96. doi: 10.1039/c5nr06353a. Epub 2015 Nov 24.
Self-assembling nanostructures in aqueous mixtures of bilayer-forming lipids and micelle-forming surfactants are relevant to in vitro studies on biological and synthetic membranes and membrane proteins. Considerable efforts are currently underway to replace conventional detergents by milder alternatives such as styrene/maleic acid (SMA) copolymers and fluorinated surfactants. However, these compounds and their nanosized assemblies remain poorly understood as regards their interactions with lipid membranes, particularly, the thermodynamics of membrane partitioning and solubilisation. Using (19)F and (31)P nuclear magnetic resonance spectroscopy, static and dynamic light scattering, and isothermal titration calorimetry, we have systematically investigated the aggregational state of a zwitterionic bilayer-forming phospholipid upon exposure to an SMA polymer with a styrene/maleic acid ratio of 3 : 1 or to a fluorinated octyl phosphocholine derivative called F(6)OPC. The lipid interactions of SMA(3 : 1) and F(6)OPC can be thermodynamically conceptualised within the framework of a three-stage model that treats bilayer vesicles, discoidal or micellar nanostructures, and the aqueous solution as distinct pseudophases. The exceptional solubilising power of SMA(3 : 1) is reflected in very low membrane-saturating and solubilising polymer/lipid molar ratios of 0.10 and 0.15, respectively. Although F(6)OPC saturates bilayers at an even lower molar ratio of 0.031, this nondetergent does not solubilise lipids even at >1000-fold molar excess, thus highlighting fundamental differences between these two types of mild membrane-mimetic systems. We rationalise these findings in terms of a new classification of surfactants based on bilayer-to-micelle transfer free energies and discuss practical implications for membrane-protein research.
自组装纳米结构在双层形成脂质和胶束形成表面活性剂的水混合物中与体外生物和合成膜和膜蛋白的研究相关。目前正在进行大量努力，用更温和的替代品替代传统的清洁剂，如苯乙烯/马来酸（SMA）共聚物和氟化表面活性剂。然而，这些化合物及其纳米级组装体对于它们与脂质膜的相互作用，特别是膜分配和溶解的热力学，仍然了解甚少。使用（19）F 和（31）P 核磁共振波谱、静态和动态光散射以及等温滴定量热法，我们系统地研究了在暴露于具有苯乙烯/马来酸比为 3:1 的 SMA 聚合物或氟化辛基磷酸胆碱衍生物 F(6)OPC 时，两性离子双层形成磷脂的聚集状态。SMA(3:1)和 F(6)OPC 的脂质相互作用可以在一个三阶段模型的框架内进行热力学概念化，该模型将双层囊泡、盘状或胶束纳米结构以及水溶液视为不同的假相。SMA(3:1)的特殊溶解能力反映在非常低的膜饱和和溶解聚合物/脂质摩尔比，分别为 0.10 和 0.15。尽管 F(6)OPC 在甚至更低的摩尔比 0.031 下饱和双层，但这种非清洁剂甚至在 1000 倍摩尔过量时也不能溶解脂质，从而突出了这两种温和的膜模拟系统之间的根本区别。我们根据双层到胶束转移自由能对这些发现进行了新的分类，并讨论了它们对膜蛋白研究的实际意义。
