Esser Alex T, Smith Kyle C, Gowrishankar T R, Weaver James C
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology Cambridge MA 02139, USA.
Technol Cancer Res Treat. 2009 Aug;8(4):289-306. doi: 10.1177/153303460900800406.
Local and drug-free solid tumor ablation by large nanosecond pulsed electric fields leads to supra-electroporation of all cellular membranes and has been observed to trigger nonthermal cell death by apoptosis. To establish pore-based effects as the underlying mechanism to inducing _apoptosis, we use a multicellular system model (spatial scale 100 microm) that has irregularly shaped liver cells and a multiscale liver tissue model (spatial scale 200 mm). Pore histograms for the multicellular model demonstrate the presence of only nanometer-sized pores due to nanosecond electric field pulses. The number of pores in the plasma membrane is such that the average tissue conductance during nanosecond electric field pulses is even higher than for longer irreversible electroporation pulses. It is shown, however, that these nanometer-sized pores, although numerous, only significantly change the permeability of the cellular membranes to small ions, but not to larger molecules. Tumor ablation by nanosecond pulsed electric fields causes small to moderate temperature increases. Thus, the underlying mechanism(s) that trigger cell death by apoptosis must be non-thermal electrical interactions, presumably leading to different ionic and molecular transport than for much longer irreversible electroporation pulses.
通过大纳秒脉冲电场进行的局部无药物实体瘤消融可导致所有细胞膜超电穿孔，并且已观察到通过凋亡引发非热细胞死亡。为了确定基于孔的效应是诱导凋亡的潜在机制，我们使用了具有不规则形状肝细胞的多细胞系统模型（空间尺度为100微米）和多尺度肝组织模型（空间尺度为200毫米）。多细胞模型的孔直方图表明，由于纳秒电场脉冲，仅存在纳米级的孔。质膜中的孔数量使得纳秒电场脉冲期间的平均组织电导率甚至高于更长时间的不可逆电穿孔脉冲。然而，结果表明，这些纳米级的孔虽然数量众多，但仅显著改变细胞膜对小离子的通透性，而对大分子则无影响。纳秒脉冲电场消融肿瘤会导致温度小幅至中度升高。因此，通过凋亡引发细胞死亡的潜在机制必定是非热电相互作用，推测这会导致与长得多的不可逆电穿孔脉冲不同的离子和分子运输。
