Life Cycle of an Electropore: Field-Dependent and Field-Independent Steps in Pore Creation and Annihilation
Life Cycle of an Electropore: Field-Dependent and Field-Independent Steps in Pore Creation and Annihilation
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DOI：
10.1007/s00232-010-9277-y
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发表时间：
2010-07-01
影响因子：
2.4
通讯作者：
Vernier, P. Thomas
中科院分区：
文献类型：
--
作者：
Levine, Zachary A.;Vernier, P. Thomas
电通透性是一种电场诱导的细胞膜屏障功能的修饰，在实验室和临床上得到了广泛的应用，但与电控细胞膜通透性相关的机制和物理结构尚未得到明确的表征。对电导和小分子传输的间接实验观察以及分子动力学模拟已经导致了在电场存在的情况下在磷脂双层中形成亲水孔的可能性增加的模型。目前可用的方法不允许对电穿孔薄膜进行直接的纳米级检查，以确认这些结构的存在。为了使穿孔模型与观察到的电透性脂质双层和细胞膜的性质相一致，我们提出了一种描述电孔形成和再密封阶段的方案。这个基于磷脂双层分子动力学模拟的电孔生命周期在电场驱动的膜重组中定义了一系列离散的步骤，导致形成头部基团衬里的水孔，然后在去掉电场后，到孔的拆除和完整双层的重新组装。利用这一方案，我们可以系统地分析电场与参与孔起始、构建和再密封的双层组分之间的相互作用。我们发现，成孔时间强烈地依赖于膜界面上的电场梯度，而成孔时间至少弱于起孔电场的大小，而且一般比成孔时间长得多。
Electropermeabilization, an electric field-induced modification of the barrier functions of the cell membrane, is widely used in laboratories and increasingly in the clinic; but the mechanisms and physical structures associated with the electromanipulation of membrane permeability have not been definitively characterized. Indirect experimental observations of electrical conductance and small molecule transport as well as molecular dynamics simulations have led to models in which hydrophilic pores form in phospholipid bilayers with increased probability in the presence of an electric field. Presently available methods do not permit the direct, nanoscale examination of electroporated membranes that would confirm the existence of these structures. To facilitate the reconciliation of poration models with the observed properties of electropermeabilized lipid bilayers and cell membranes, we propose a scheme for characterizing the stages of electropore formation and resealing. This electropore life cycle, based on molecular dynamics simulations of phospholipid bilayers, defines a sequence of discrete steps in the electric field-driven restructuring of the membrane that leads to the formation of a head group-lined, aqueous pore and then, after the field is removed, to the dismantling of the pore and reassembly of the intact bilayer. Utilizing this scheme we can systematically analyze the interactions between the electric field and the bilayer components involved in pore initiation, construction and resealing. We find that the pore creation time depends strongly on the electric field gradient across the membrane interface and that the pore annihilation time is at least weakly dependent on the magnitude of the pore-initiating electric field and, in general, much longer than the pore creation time.