Nanopore-facilitated, voltage-driven phosphatidylserine translocation in lipid bilayers -: in cells and in silico
Nanopore-facilitated, voltage-driven phosphatidylserine translocation in lipid bilayers -: in cells and in silico
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DOI：
10.1088/1478-3975/3/4/001
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发表时间：
2006-12-01
期刊：
影响因子：
2
通讯作者：
Tieleman, D. Peter
中科院分区：
文献类型：
--
作者：
Vernier, P. Thomas;Ziegler, Matthew J.;Tieleman, D. Peter
纳秒、兆伏每米的脉冲——比用于将通常排除的物质引入生物细胞的电穿孔脉冲更高的功率但总能量更低——产生大的细胞内电场，而不会破坏性地对质膜充电。哺乳动物细胞的纳电脉冲扰动导致磷脂酰丝氨酸 (PS) 易位到细胞外表面、细胞内钙释放，并且在某些细胞类型中随后进展为细胞凋亡。本文提出的脉冲电场中膜的实验观察和分子动力学 (MD) 模拟支持这样的假设：纳米电脉冲诱导的 PS 外化是由脉冲期间跨脂质双层出现的电势驱动的，并且即使在短至 3 ns 的脉冲期间也会通过膜的孔化来促进。超生理电场中磷脂双层的 MD 模拟显示，纳秒时间尺度上的 PS 外化和膜孔形成之间存在紧密关联，这与纳秒电脉冲暴露后电透化和阳极定向 PS 易位的实验证据一致，表明纳米电穿孔和纳秒 PS 外化的分子机制：带负电的 PS 头基沿着纳米直径电孔表面的电泳迁移，由场驱动的水偶极子排列引发。膜界面。
Nanosecond, megavolt-per-meter pulses-higher power but lower total energy than the electroporative pulses used to introduce normally excluded material into biological cells-produce large intracellular electric fields without destructively charging the plasma membrane. Nanoelectropulse perturbation of mammalian cells causes translocation of phosphatidylserine (PS) to the outer face of the cell, intracellular calcium release, and in some cell types a subsequent progression to apoptosis. Experimental observations and molecular dynamics (MD) simulations of membranes in pulsed electric fields presented here support the hypothesis that nanoelectropulse-induced PS externalization is driven by the electric potential that appears across the lipid bilayer during a pulse and is facilitated by the poration of the membrane that occurs even during pulses as brief as 3 ns. MD simulations of phospholipid bilayers in supraphysiological electric fields show a tight association between PS externalization and membrane pore formation on a nanosecond time scale that is consistent with experimental evidence for electropermeabilization and anode-directed PS translocation after nanosecond electric pulse exposure, suggesting a molecular mechanism for nanoelectroporation and nanosecond PS externalization: electrophoretic migration of the negatively charged PS head group along the surface of nanometer-diameter electropores initiated by field-driven alignment of water dipoles at the membrane interface.