Sieni Elisabetta, Dettin Monica, Zamuner Annj, Conconi Maria Teresa, Bazzolo Bianca, Balducci Cristian, Di Barba Paolo, Forzan Michele, Lamberti Patrizia, Mognaschi Maria Evelina
Department of Theoretical and Applied Sciences, University of Insubria, Via Dunant 3, 21100 Varese, Italy.
Italian Interuniversity Center ICEMB (Interaction between Electromagnetic Fields and Biosystems), DIET University of Genoa, 16145 Genoa, Italy.
Bioengineering (Basel). 2023 Sep 8;10(9):1062. doi: 10.3390/bioengineering10091062.
Finite element analysis is used in this study to investigate the effect of media inhomogeneity on the electric field distribution in a sample composed of cells and their extracellular matrix. The sample is supposed to be subjected to very high pulsed electric field. Numerically computed electric field distribution and transmembrane potential at the cell membrane in electroporation conditions are considered in order to study cell behavior at different degrees of inhomogeneity. The different inhomogeneity grade is locally obtained using a representative model of fixed volume with cell-cell distance varying in the range of 1-283 um. The conductivity of the extracellular medium was varied between plain collagen and a gel-like myxoid matrix through combinations of the two, i.e., collagen and myxoid. An increase in the transmembrane potential was shown in the case of higher aggregate. The results obtained in this study show the effect of the presence of the cell aggregates and collagen on the transmembrane potential. In particular, by increasing the cell aggregation in the two cases, the transmembrane potential increased. Finally, the simulation results were compared to experimental data obtained by culturing HCC1954 cells in a hyaluronic acid-based scaffold. The experimental validation confirmed the behavior of the transmembrane potential in presence of the collagen: an increase in electroporation at a lower electric field intensity was found for the cells cultured in the scaffolds where there is the formation of collagen areas.
本研究采用有限元分析方法，以研究介质不均匀性对由细胞及其细胞外基质组成的样本中电场分布的影响。假设该样本受到非常高的脉冲电场作用。为了研究在不同程度的不均匀性下细胞的行为，考虑了在电穿孔条件下数值计算得到的电场分布和细胞膜处的跨膜电位。使用具有固定体积的代表性模型局部获得不同的不均匀性等级，其中细胞间距离在1 - 283微米范围内变化。通过将两种物质（即胶原蛋白和类黏液基质）组合，使细胞外介质的电导率在纯胶原蛋白和凝胶状类黏液基质之间变化。在较高聚集度的情况下，跨膜电位显示出增加。本研究获得的结果表明了细胞聚集体和胶原蛋白的存在对跨膜电位的影响。特别是，在这两种情况下，通过增加细胞聚集度，跨膜电位增加。最后，将模拟结果与通过在基于透明质酸的支架中培养HCC1954细胞获得的实验数据进行比较。实验验证证实了在存在胶原蛋白的情况下跨膜电位的行为：在形成胶原蛋白区域的支架中培养的细胞，在较低电场强度下电穿孔增加。
