Stability of Biological Membranes upon Mechanical Indentation

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普遍存在，众多生物学功能依赖于脂质膜的机械响应。近年来，通过力谱学研究表明，双层膜堆叠的逐步断裂过程得以捕捉，且避免了基底效应。然而，关于膜堆叠效应及其断裂过程的精确分子机制尚不明确。在本研究中，我们运用原子和粗粒化力钳分子动力学模拟，评估了机械压痕对堆叠双层膜和单层膜的影响。我们的模拟表明，断裂过程遵循力激活的势垒跨越定律，多层膜的堆叠有助于其稳定性。断裂时间遵循对数正态分布，这允许将膜破裂过程视为孔隙生长过程。压痕亲疏水性决定了孔隙形成类型、首选驻留区域以及双层膜对破裂的抵抗力。我们的研究结果为理解脂质膜塑性破裂背后的纳米力学提供了更深入的认识。