The formation of transient pores in their membranes is a well-known mechanism of permeabilization of cells exposed to high-intensity electric pulses. However, the formation of such pores is not able to explain all aspects of the so-called electroporation phenomenon. In particular, the reasons for sustained permeability of cell membranes, persisting long after the pulses’ application, remain elusive. The complete resealing of cell membranes takes indeed orders of magnitude longer than the time for electropore closure as reported from molecular dynamics (MD) investigations. Lipid peroxidation has been suggested as a possible mechanism to explain the sustainable permeability of cell membranes. However, theoretical investigations of membrane lesions containing excess amounts of hydroperoxides have shown that the conductivities of such lesions were not high enough to account for the experimental measurements. Here, expanding on these studies, we investigate quantitatively the permeability of cell membrane lesions that underwent secondary oxidation. MD simulations and free energy calculations of lipid bilayers show that such lesions provide a better model of post-pulse permeable and conductive electropermeabilized cells. These results are further discussed in the context of sonoporation and ferroptosis, respectively a procedure and a phenomenon, among others, in which, alike electroporation, substantial lipid oxidation might be triggered.

细胞膜中瞬时孔的形成是暴露于高强度电脉冲的细胞通透化的众所周知的机制。然而，这种孔的形成并不能解释所谓的电穿孔现象的所有方面。特别是，在施加脉冲后很长时间内细胞膜持续通透性的原因仍然难以捉摸。细胞膜的完全重新密封确实比分子动力学 (MD) 研究报告的电孔闭合时间长几个数量级。脂质过氧化被认为是解释细胞膜可持续通透性的一种可能机制。然而，对含有过量氢过氧化物的膜损伤的理论研究表明，这种损伤的电导率不足以解释实验测量结果。在这里，扩展这些研究，我们定量研究了经历二次氧化的细胞膜病变的渗透性。脂质双层的 MD 模拟和自由能计算表明，此类病变提供了更好的脉冲后渗透性和导电性电渗透性细胞模型。这些结果在声穿孔和铁死亡的背景下进一步讨论，分别是一种程序和现象，其中，与电穿孔一样，可能会触发大量的脂质氧化。我们定量研究了经历二次氧化的细胞膜损伤的渗透性。脂质双层的 MD 模拟和自由能计算表明，此类病变提供了更好的脉冲后渗透性和导电性电渗透性细胞模型。这些结果在声穿孔和铁死亡的背景下进一步讨论，分别是一种程序和现象，其中，与电穿孔一样，可能会触发大量的脂质氧化。我们定量研究了经历二次氧化的细胞膜损伤的渗透性。脂质双层的 MD 模拟和自由能计算表明，此类病变提供了更好的脉冲后渗透性和导电性电渗透性细胞模型。这些结果在声穿孔和铁死亡的背景下进一步讨论，分别是一种程序和现象，其中，与电穿孔一样，可能会触发大量的脂质氧化。