Theoretical modeling of the effects of shock duration, frequency, and strength on the degree of electroporation
Theoretical modeling of the effects of shock duration, frequency, and strength on the degree of electroporation
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DOI：
10.1016/s0302-4598(00)00066-0
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发表时间：
2000-06-01
影响因子：
5
通讯作者：
Krassowska, W
中科院分区：
文献类型：
--
作者：
Bilska, AO;DeBruin, KA;Krassowska, W
电穿孔正成为将生物活性化合物引入活细胞中的越来越重要的工具，然而该技术的有效性可能较低，特别是在体内。提高成功率的一种方法是优化电击方案，但实验研究成本高、耗时，并且只能间接测量孔隙的产生。另外，本研究模型的电穿孔在两种几何形状，一个空间夹膜和一个单一的细胞，并调查脉冲持续时间，频率，形状和强度的影响。孔的产生由来自Smoluchowski方程的一阶微分方程描述。膜和细胞都暴露于不同持续时间的单相和双相冲击（膜，10 μ s-100 s;细胞，0.1 μ s-200 ms）和不同频率的单相和双相脉冲串（膜，50 Hz-4 kHz;细胞，200 kHz-6 MHz）。通过孔面积分数（FPA）测量每次摇动的有效性。结果表明，FPA仅在很窄的范围内（膜，约为1 ms;细胞，约为0.25 μ s）对冲击持续时间敏感。FPA对冲击强度和脉冲串频率敏感，随冲击强度线性增加，随频率缓慢下降。在所有情况下，双相电击至少与双相电击一样有效，这意味着改变双相脉冲串的强度和频率是控制毛孔形成的最有效方法。(C)2000 Elsevier Science S.A. All rights reserved.
Electroporation is becoming an increasingly important tool for introducing biologically active compounds into living cells, yet the effectiveness of this technique can be low, particularly in vivo. One way to improve the success rate is to optimize the shock protocols, but experimental studies are costly, time consuming, and yield only an indirect measurement of pore creation. Alternatively, this study models electroporation in two geometries, a space-clamped membrane and a single cell, and investigates the effects of pulse duration, frequency, shape, and strength. The creation of pores is described by a first order differential equation derived from the Smoluchowski equation. Both the membrane and the cell are exposed to monophasic and biphasic shooks of varying duration (membrane, 10 mus-100 s; cell, 0.1 mus-200 ms) and to trains of monophasic and biphasic pulses of varying frequency (membrane, 50 Hz-4 kHz; cell, 200 kHz-6 MHz). The effectiveness of each shook is measured by the fractional pore: area (FPA). The results indicate that FPA is sensitive to shock duration only in a very narrow range (membrane, approximate to 1 ms; cell, approximate to 0.25 mus). In contrast, FPA is sensitive to shock strength and frequency of the pulse train, increasing linearly with shuck strength and decreasing slowly with frequency. In all cases, monophasic shooks were at least as effective as biphasic shocks, implying that varying the strength and frequency of a monophasic pulse train is the most effective way to control the creation of pores. (C) 2000 Elsevier Science S.A. All rights reserved.