Integrated Bioscience Section, Graduate School of Science and Technology , Shizuoka University , Shizuoka 422-8529 , Japan.
Theoretical Problem Center of Physico-Chemical Pharmacology , Russian Academy of Sciences , Kosugina, 4 , 117977 Moscow , Russia.
J Phys Chem B. 2019 Jun 6;123(22):4645-4652. doi: 10.1021/acs.jpcb.9b01562. Epub 2019 May 22.
The transbilayer asymmetry of the biomembrane is generated due to the differences in lipid and protein compositions between two leaflets, which plays important roles in physiological functions. However, transbilayer asymmetry can also be originated due to a nonequal number of lipids or proteins in each leaflet, which has not been well recognized. Therefore, to shed light on this field, here we generated theoretical models for the effect of transbilayer asymmetry originated from the differences in the number of lipids and peptides in each leaflet on the state of lipid bilayers. The first model described the effect of asymmetric lipid distribution on the state of lipid bilayers. We obtained theoretical equations for the fractional change in area per lipid in both leaflets as a function of the ratio of the number of lipids in each leaflet, which agreed with the molecular dynamics simulation results quantitatively. Results indicated that tensions in both leaflets are opposite in direction, and their magnitude is the same. We also performed experiments on the effect of lipid insertion in the outer leaflet on the fractional change in area per lipid. These results agreed quantitatively with the values predicted by the above model. The second model described the effect of asymmetric distribution of peptides on the state of lipid bilayers. We obtained theoretical equations for the area per lipid in both leaflets as a function of the surface concentration of peptides located only in the outer leaflet, which agreed with the results of the antimicrobial peptide magainin 2-induced area change.
生物膜的跨膜不对称性是由于两个叶层之间的脂质和蛋白质组成的差异产生的，它在生理功能中起着重要作用。然而，跨膜不对称性也可能由于每个叶层中的脂质或蛋白质数量不均等而产生，这一点尚未得到很好的认识。因此，为了阐明这一领域，我们在这里建立了理论模型，以研究由于每个叶层中脂质和肽的数量差异而导致的跨膜不对称性对脂质双层状态的影响。第一个模型描述了不对称脂质分布对脂质双层状态的影响。我们得到了每个叶层中脂质数量比值的函数的两个叶层中每个脂质的面积分数变化的理论方程，这与分子动力学模拟结果在数量上是一致的。结果表明，两个叶层的张力方向相反，大小相同。我们还对外层脂质中插入脂质对每个脂质面积分数变化的影响进行了实验。这些结果与上述模型预测的值在数量上是一致的。第二个模型描述了肽的不对称分布对脂质双层状态的影响。我们得到了每个叶层中脂质的面积与仅位于外层的肽的表面浓度的函数的理论方程，这与抗菌肽 magainin 2 诱导的面积变化的结果一致。
