Aslam Muhammad Awais, Riaz Kashif, Mahmood Muhammad Qasim, Zubair Muhammad
Electrical Engineering Department, Information Technology University 54000 Lahore Pakistan
RSC Adv. 2019 Dec 16;9(71):41518-41530. doi: 10.1039/c9ra07428g. eCollection 2019 Dec 13.
Electroporation has offered important biomedical applications in electrochemotherapy, tissue ablation and gene editing recently. Time and computation efficient analytical and numerical models should be developed to understand the differential effects of electroporation on normal and cancer cells. In this work, we present a hybrid analytical-numerical approach to investigate the behavior of normal and cancer cells under electroporation. We have compared the human breast cancer cell (MCF-7) and non-tumorigenic human breast cell (MCF-10A) under electroporation in terms of change in transmembrane voltage and pore formation on cell surface. The effects of electric pulse time, amplitude and membrane conductivity variation are analyzed in a systematic manner. To accelerate the calculation of transmembrane voltage, we have introduced a simple Multilayer Electric Potential Model (MEPM) which calculates the potential distribution across the cell analytically. The MEPM calculates electric potential distribution across a biological cell sandwiched between two semi-circular electrodes held at fixed potential, by solving the Laplace's equation over an equivalent planar, multilayer geometry. The MEPM model is then used in a Finite Element Method (FEM) based numerical model of electroporation. Transmembrane voltage and pore density for electroporated MCF-10A are estimated to be 1.31 V and 2.98 × 10 m respectively, and for MCF-7 the estimated values are 0.53 V and 1.93 × 10 m, respectively. Our results suggest that under electroporation, the cancer cell's membrane get much more permeabilized than its counterpart normal cell even at small values of transmembrane voltage. This work provides a theoretical basis for further experimental exploration of electroporation process in cancer therapy, and serves as a design tool for performance optimization.
近年来，电穿孔技术在电化学疗法、组织消融和基因编辑等生物医学领域展现出重要应用。为了理解电穿孔对正常细胞和癌细胞的不同作用，应开发高效省时的分析和数值模型。在这项工作中，我们提出了一种混合分析-数值方法来研究电穿孔作用下正常细胞和癌细胞的行为。我们比较了人乳腺癌细胞（MCF-7）和非致瘤性人乳腺细胞（MCF-10A）在电穿孔过程中的跨膜电压变化和细胞表面孔形成情况。系统分析了电脉冲时间、幅度和膜电导率变化的影响。为了加速跨膜电压的计算，我们引入了一个简单的多层电势模型（MEPM），该模型通过解析计算细胞上的电势分布。MEPM通过在等效的平面多层几何结构上求解拉普拉斯方程，计算夹在两个固定电势的半圆形电极之间的生物细胞上的电势分布。然后将MEPM模型用于基于有限元方法（FEM）的电穿孔数值模型中。电穿孔后的MCF-10A的跨膜电压和孔密度估计分别为1.31 V和2.98×10 ，而MCF-7的估计值分别为0.53 V和1.93×10 。我们的结果表明，在电穿孔作用下，即使在跨膜电压值较小的情况下，癌细胞膜的通透性也比其对应的正常细胞高得多。这项工作为癌症治疗中电穿孔过程的进一步实验探索提供了理论基础，并作为性能优化的设计工具。
