Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation.
Modeling of Transmembrane Potential in Realistic Multicellular Structures before Electroporation.
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DOI：
10.1016/j.bpj.2016.10.005
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发表时间：
2016-11
影响因子：
3.4
通讯作者：
T. Murovec;Daniel C. Sweeney;Eduardo L. Latouche;R. Davalos;C. Brosseau
中科院分区：
文献类型：
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作者：
T. Murovec;Daniel C. Sweeney;Eduardo L. Latouche;R. Davalos;C. Brosseau
研究脉冲电场处理生物细胞过程中产生的跨膜电位（TMP）的方法很多。从简单的分析模型到需要大量计算资源的更复杂的数值模型，已经使用了各种方法来模拟多细胞环境。细胞已经被建模为二维的简单形状以及试图复制现实细胞形状的更复杂的几何形状。在这项研究中，我们描述了一种从荧光显微镜图像中提取逼真的细胞形态，以生成用于开发二维有限元模型的分段连续网格的方法。针对由临床不可逆电穿孔治疗激发的两组脉冲参数，分析在紧密堆积的细胞中诱导的预电穿孔TMP。我们表明，高频双极脉冲序列是更好的，更均匀地提高TMP的紧密包装的细胞比传统的不可逆电穿孔脉冲序列的模拟电穿孔阈值，在较大的外加电位为代价。我们的研究结果表明，我们的方法的可行性，并强调在用于研究暴露于电场的生物组织的响应的数值模型中考虑多细胞效应的重要性。
Many approaches for studying the transmembrane potential (TMP) induced during the treatment of biological cells with pulsed electric fields have been reported. From the simple analytical models to more complex numerical models requiring significant computational resources, a gamut of methods have been used to recapitulate multicellular environments in silico. Cells have been modeled as simple shapes in two dimensions as well as more complex geometries attempting to replicate realistic cell shapes. In this study, we describe a method for extracting realistic cell morphologies from fluorescence microscopy images to generate the piecewise continuous mesh used to develop a finite element model in two dimensions. The preelectroporation TMP induced in tightly packed cells is analyzed for two sets of pulse parameters inspired by clinical irreversible electroporation treatments. We show that high-frequency bipolar pulse trains are better, and more homogeneously raise the TMP of tightly packed cells to a simulated electroporation threshold than conventional irreversible electroporation pulse trains, at the expense of larger applied potentials. Our results demonstrate the viability of our method and emphasize the importance of considering multicellular effects in the numerical models used for studying the response of biological tissues exposed to electric fields.