Molecular Biomechanics Group , Heidelberg Institute for Theoretical Studies , 69118 Heidelberg , Germany.
Max Planck Tandem Group in Computational Biophysics , University of Los Andes , 111711 Bogotá , Colombia.
J Phys Chem B. 2018 Jul 19;122(28):7073-7079. doi: 10.1021/acs.jpcb.8b01861. Epub 2018 Jul 5.
Mechanical perturbations are ubiquitous in living cells, and many biological functions are dependent on the mechanical response of lipid membranes. Recent force-spectroscopy studies have captured the stepwise fracture of stacks of bilayers, avoiding substrate effects. However, the effect of stacking bilayers, as well as the exact molecular mechanism of the fracture process, is unknown. Here, we use atomistic and coarse-grained force-clamp molecular dynamics simulation to assess the effects of mechanical indentation on stacked and single bilayers. Our simulations show that the rupture process obeys the laws of force-activated barrier crossing, and stacking multiple membranes stabilizes them. The rupture times follow a log-normal distribution which allows the interpretation of membrane rupture as a pore-growth process. Indenter hydrophobicity determines the type of pore formation, the preferred dwelling region, and the resistance of the bilayer against rupture. Our results provide a better understanding of the nanomechanics underlying the plastic rupture of lipid membranes.
机械扰动在活细胞中无处不在，许多生物功能依赖于脂质膜的机械响应。最近的力谱研究捕获了双层堆栈的逐步断裂，避免了基底效应。然而，堆叠双层的影响以及断裂过程的确切分子机制尚不清楚。在这里，我们使用原子和粗粒力钳分子动力学模拟来评估机械压痕对堆叠和单层双层的影响。我们的模拟表明，破裂过程遵循力激活势垒穿越的规律，并且堆叠多个膜会使其稳定。破裂时间遵循对数正态分布，这允许将膜破裂解释为孔生长过程。压头疏水性决定了孔形成的类型、优先停留区域以及双层抵抗破裂的阻力。我们的结果提供了对脂质膜塑性破裂的纳米力学的更好理解。
