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<p>Electroporation has advanced significantly in biomedical applications, particularly in tissue ablation. While the influence of individual cellular features, such as cell size and nucleus-to-cytoplasm ratio, on ablation is recognized, this study highlights the key role of the cell grouping factor, namely cell density. Experiments using 2D cell monolayers demonstrated a density-dependent ablation effect: higher cell density significantly elevates resistance to electroporation, evident from reduced ablation areas and ~30% higher lethal electric thresholds (LETs). To explain this, a cell-cell proximity electroporation model was established representing cell density by intercellular distance and degree of containment. It indicated significant inhibition when cells were closely spaced (0-2 µm), with lower pore density and reduced pore area ratios (PARs). This inhibitory effect decays logarithmically as spacing increases, persisting over several cell diameters. Furthermore, fully surrounded cells exhibit a 33% lower PAR than isolated cells, consistent with the observed LET gap between high- and low-density populations. As such, the shielding effect from neighboring cells leads to the density-dependent electroporation at cellular scale and may therefore account for the density-dependent ablation observed at tissue scale. In light of this, considering tissue-specific cell density are critical for better mimicking in vivo conditions, and improving precision in electroporation-based tissue therapies.</p>

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Role of cell density and proximity in electroporation for tissue ablation

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月20日

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  • Lujia Ding,
  • Mike A. J. Moser,
  • Bing Zhang,
  • Chris Zhang,
  • Ningning Hu

摘要

Electroporation has advanced significantly in biomedical applications, particularly in tissue ablation. While the influence of individual cellular features, such as cell size and nucleus-to-cytoplasm ratio, on ablation is recognized, this study highlights the key role of the cell grouping factor, namely cell density. Experiments using 2D cell monolayers demonstrated a density-dependent ablation effect: higher cell density significantly elevates resistance to electroporation, evident from reduced ablation areas and ~30% higher lethal electric thresholds (LETs). To explain this, a cell-cell proximity electroporation model was established representing cell density by intercellular distance and degree of containment. It indicated significant inhibition when cells were closely spaced (0-2 µm), with lower pore density and reduced pore area ratios (PARs). This inhibitory effect decays logarithmically as spacing increases, persisting over several cell diameters. Furthermore, fully surrounded cells exhibit a 33% lower PAR than isolated cells, consistent with the observed LET gap between high- and low-density populations. As such, the shielding effect from neighboring cells leads to the density-dependent electroporation at cellular scale and may therefore account for the density-dependent ablation observed at tissue scale. In light of this, considering tissue-specific cell density are critical for better mimicking in vivo conditions, and improving precision in electroporation-based tissue therapies.