Harvard-M.I.T. Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Biochem Biophys Res Commun. 2011 Aug 19;412(1):8-12. doi: 10.1016/j.bbrc.2011.06.171. Epub 2011 Jul 2.
Recently there has been intense and growing interest in the non-thermal biological effects of nanosecond electric pulses, particularly apoptosis induction. These effects have been hypothesized to result from the widespread creation of small, lipidic pores in the plasma and organelle membranes of cells (supra-electroporation) and, more specifically, ionic and molecular transport through these pores. Here we show that transport occurs overwhelmingly after pulsing. First, we show that the electrical drift distance for typical charged solutes during nanosecond pulses (up to 100 ns), even those with very large magnitudes (up to 10 MV/m), ranges from only a fraction of the membrane thickness (5 nm) to several membrane thicknesses. This is much smaller than the diameter of a typical cell (∼16 μm), which implies that molecular drift transport during nanosecond pulses is necessarily minimal. This implication is not dependent on assumptions about pore density or the molecular flux through pores. Second, we show that molecular transport resulting from post-pulse diffusion through minimum-size pores is orders of magnitude larger than electrical drift-driven transport during nanosecond pulses. While field-assisted charge entry and the magnitude of flux favor transport during nanosecond pulses, these effects are too small to overcome the orders of magnitude more time available for post-pulse transport. Therefore, the basic conclusion that essentially all transmembrane molecular transport occurs post-pulse holds across the plausible range of relevant parameters. Our analysis shows that a primary direct consequence of nanosecond electric pulses is the creation (or maintenance) of large populations of small pores in cell membranes that govern post-pulse transmembrane transport of small ions and molecules.
最近，人们对纳秒电脉冲的非热生物效应，特别是细胞凋亡诱导，产生了浓厚且日益增长的兴趣。这些效应被假设是由于细胞的质膜和细胞器膜中广泛产生小的脂质孔（超电穿孔），更具体地说，是由于离子和分子通过这些孔的传输而产生的。在这里，我们证明了传输主要发生在脉冲之后。首先，我们表明，在纳秒脉冲期间（高达 100ns），即使对于具有非常大绝对值（高达 10MV/m）的典型带电溶质，其电漂移距离也仅在膜厚度的一小部分（5nm）到几个膜厚度之间。这远小于典型细胞的直径（约 16μm），这意味着纳秒脉冲期间的分子漂移传输必然是最小的。这种含义不依赖于关于孔密度或通过孔的分子通量的假设。其次，我们表明，通过最小尺寸的孔进行脉冲后扩散而导致的分子传输比纳秒脉冲期间的电漂移驱动传输大几个数量级。虽然场辅助电荷进入和通量的大小有利于纳秒脉冲期间的传输，但这些效应太小，无法克服脉冲后传输可用的时间数量级更大。因此，在合理的相关参数范围内，基本结论是，基本上所有跨膜分子传输都发生在脉冲之后。我们的分析表明，纳秒电脉冲的一个主要直接后果是在细胞膜中创建（或维持）大量小孔，这些小孔控制着小离子和分子的脉冲后跨膜传输。
