Department of Biochemistry and Biophysics, Stockholm University, Stockholm, Sweden and Department of Materials and Environmental Chemistry, Stockholm University, Stockholm, Sweden.
Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden.
Soft Matter. 2019 Jan 28;15(4):792-802. doi: 10.1039/c8sm02133c. Epub 2019 Jan 15.
Cardiolipin is a non-bilayer phospholipid with a unique dimeric structure. It localizes to negative curvature regions in bacteria and is believed to stabilize respiratory chain complexes in the highly curved mitochondrial membrane. Cardiolipin's localization mechanism remains unresolved, because important aspects such as the structural basis and strength for lipid curvature preferences are difficult to determine, partly due to the lack of efficient simulation methods. Here, we report a computational approach to study curvature preferences of cardiolipin by simulated membrane buckling and quantitative modeling. We combine coarse-grained molecular dynamics with simulated buckling to determine the curvature preferences in three-component bilayer membranes with varying concentrations of cardiolipin, and extract curvature-dependent concentrations and lipid acyl chain order parameter profiles. Cardiolipin shows a strong preference for negative curvatures, with a highly asymmetric chain order parameter profile. The concentration profiles are consistent with an elastic model for lipid curvature sensing that relates lipid segregation to local curvature via the material constants of the bilayers. These computations constitute new steps to unravel the molecular mechanism by which cardiolipin senses curvature in lipid membranes, and the method can be generalized to other lipids and membrane components as well.
心磷脂是一种具有独特二聚体结构的非双层磷脂。它定位于细菌中的负曲率区域，被认为可以稳定高度弯曲的线粒体膜中的呼吸链复合物。心磷脂的定位机制仍未解决，因为脂质曲率偏好的结构基础和强度等重要方面难以确定，部分原因是缺乏有效的模拟方法。在这里，我们报告了一种通过模拟膜弯曲和定量建模来研究心磷脂曲率偏好的计算方法。我们将粗粒分子动力学与模拟弯曲相结合，以确定具有不同心磷脂浓度的三组分双层膜中的曲率偏好，并提取曲率相关的浓度和脂质酰基链有序参数分布。心磷脂强烈倾向于负曲率，具有高度不对称的链有序参数分布。浓度分布与脂质曲率感应的弹性模型一致，该模型通过双层的材料常数将脂质分离与局部曲率联系起来。这些计算为揭示心磷脂在脂质膜中感应曲率的分子机制迈出了新的一步，该方法也可以推广到其他脂质和膜成分。
