Department of Mechanical Science & Bioengineering, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka, Japan.
Graduate School of Technology, Industrial and Social Sciences, Tokushima University, Tokushima, Japan.
J Biomol Struct Dyn. 2024 Oct;42(17):9159-9166. doi: 10.1080/07391102.2023.2250447. Epub 2023 Sep 1.
Water permeation through phospholipid/cholesterol bilayers is the key to understanding tension-induced rupture of biological cell membranes. We performed molecular dynamics simulations of stretched phospholipid/cholesterol bilayers to investigate changes in the free energy profile of water molecules across the bilayer and the lipid structure responsible for water permeation. We modeled stretching of the bilayer by applying areal strain. In stretched phospholipid/cholesterol bilayers, the hydrophobic tail of the phospholipids became disordered and the free energy barrier to water permeation decreased. Upon exceeding the critical areal strain, a phase transition to an interdigitated gel phase occurred before rupture, and the hydrophobic tail ordering as well as the free energy barrier were restored. In pure phospholipid bilayers, we did not observe such recoveries. These transient recoveries in the phospholipid/cholesterol bilayer suppressed water permeation and membrane rupture, followed by an increase in the critical areal strain at which the bilayer ruptured. This result agrees with experimental results and provides a reasonable molecular mechanism for the toughness of phospholipid/cholesterol bilayers under tension.Communicated by Ramaswamy H. Sarma.
水通过磷脂/胆固醇双层的渗透是理解生物细胞膜张力诱导破裂的关键。我们对拉伸的磷脂/胆固醇双层进行了分子动力学模拟，以研究水分子穿过双层的自由能分布和负责渗透的脂质结构的变化。我们通过施加面应变来模拟双层的拉伸。在拉伸的磷脂/胆固醇双层中，磷脂的疏水尾部变得无序，水渗透的自由能障碍降低。当超过临界面应变时，在破裂之前发生交错凝胶相的相变，疏水尾部有序化和自由能障碍得到恢复。在纯磷脂双层中，我们没有观察到这种恢复。磷脂/胆固醇双层中的这些瞬时恢复抑制了水的渗透和膜的破裂，随后在双层破裂时临界面应变增加。这一结果与实验结果一致，并为张力下磷脂/胆固醇双层的韧性提供了合理的分子机制。由 Ramaswamy H. Sarma 交流。
