Department of Biological Sciences, Bethlehem, Pennsylvania; Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania.
Department of Biological Sciences, Bethlehem, Pennsylvania; Department of Chemistry, Lehigh University, Bethlehem, Pennsylvania.
Biophys J. 2021 Nov 16;120(22):5041-5059. doi: 10.1016/j.bpj.2021.10.009. Epub 2021 Oct 13.
It has been proposed that the surface tension difference between leaflets (or differential stress) in asymmetric bilayers is generally nonvanishing. This implies that there is no unique approach to generate initial conditions for simulations of asymmetric bilayers in the absence of experimentally derived constraints. Current generation methods include individual area per lipid (APL) based, leaflet surface area (SA) matching, and zero leaflet tension based (0-DS). This work adds a bilayer-based approach that aims for achieving partial chemical equilibrium by interleaflet switching of selected lipids via P2 periodic boundary conditions. Based on a recently proposed theoretical framework, we obtained expressions for tensions in asymmetric bilayers from both the bending and area strains. We also developed a quantitative measure for the energetic penalty from the differential stress. The impacts of APL-, SA-, and 0-DS-based approaches on mechanical properties are assessed for two different asymmetric bilayers. The lateral pressure profile and its moments differ significantly for each method, whereas the area compressibility modulus is relatively insensitive. Application of P2 periodic boundary conditions (APL/P2, SA/P2, and 0-DS/P2) results in better agreement in mechanical properties between asymmetric bilayers generated by APL-, SA-, and 0-DS-based approaches, in which changes are the smallest for bilayers from the SA-based method. The estimated differential stress from the theory shows good agreement with that from the simulations. These simulation results and the good agreement between the predicted and observed differential stress further support the theoretical framework in which bilayer mechanical properties are outcomes of the interplay between intrinsic bending and asymmetric lipid packing. Based on the simulation results and theoretical predictions, the SA/P2-based, or at least the SA-based (when the differential stress is small), approach is recommended as a practical method for developing initial conditions for asymmetric bilayer simulations.
有人提出，不对称双层膜中小叶（或差应力）之间的表面张力差一般不为零。这意味着，在没有实验得出的约束条件的情况下，没有一种独特的方法可以为不对称双层膜的模拟生成初始条件。目前的生成方法包括基于每个脂质的单位面积（APL）、小叶表面积（SA）匹配和零小叶张力（0-DS）。这项工作增加了一种基于双层膜的方法，该方法通过 P2 周期性边界条件，通过小叶间的交换来实现部分化学平衡。基于最近提出的理论框架，我们从弯曲应变和面积应变中得到了不对称双层膜中张力的表达式。我们还开发了一种用于衡量差应力的能量代价的定量度量方法。我们评估了基于 APL、SA 和 0-DS 的方法对两种不同不对称双层膜的机械性能的影响。对于每种方法，侧向压力分布及其矩都有很大的差异，而面积压缩模量则相对不敏感。应用 P2 周期性边界条件（APL/P2、SA/P2 和 0-DS/P2）会导致基于 APL、SA 和 0-DS 的方法生成的不对称双层膜之间的机械性能更一致，其中基于 SA 的方法生成的双层膜变化最小。理论预测的差应力与模拟结果吻合较好。这些模拟结果和理论预测之间的良好一致性进一步支持了这样一种理论框架，即双层膜的机械性能是内在弯曲和不对称脂质堆积相互作用的结果。基于模拟结果和理论预测，推荐使用 SA/P2 或至少 SA（当差应力较小时）为不对称双层膜模拟生成初始条件的实用方法。
