BACKGROUND After the discovery of membrane-reversible electroporation decades ago, the procedure has been used extensively in biology, biotechnology and medicine. The research on the basic mechanism has increasingly attracted attention. Although most research has focused on models that consider all atomic and molecular interactions and much atomic-level information can be obtained, the huge computational demand limits the models to simulations of only a few nanometers on the spatial scale and a few nanoseconds on the time scale. In order to more comprehensively study the reversible electroporation mechanism of phospholipid membrane on the nanoscale and at longer time intervals of up to 100 ns, we developed a dipalmitoylphosphatidylcholine (DPPC) phospholipid membrane model with the coarse-grained Martini force field. The model was tested by separately examining the morphology of the phospholipid membrane, the hydrophilic channel size, the distribution of the voltage potential on both sides of the membrane, and the movement of water molecules and ions during electroporation. RESULTS The results showed that the process went through several stages: (1) the formation of the pore with defects originating on the surface. (2) The maintenance of the pore. The defects expanded to large pores and the size remains unchanged for several nanoseconds. (3) Pore healing stage due to self-assembly. Phospholipid membrane shrunk and the pore size decreased until completely closed. The pores were not circular in cross-section for most of the time and the potential difference across the membrane decreased dramatically after the pores formed, with almost no restoration of membrane integrity even when the pores started to close. CONCLUSIONS The mechanism of the reversible electroporation process on the nanoscale level, including defects, expansion, stability, and pore closing stages on a longer time scale of up to 100 ns was demonstrated more comprehensively with the coarse-grained Martini force field, which took both the necessary molecular information and the calculation efficiency into account.

中文翻译：

---

马蒂尼力场可逆电穿孔的分子动力学模拟。

背景技术几十年前发现膜可逆电穿孔后，该程序已广泛用于生物学，生物技术和医学中。基本机理的研究日益引起人们的关注。尽管大多数研究都集中在考虑所有原子和分子相互作用的模型上，并且可以获得很多原子级信息，但是巨大的计算需求将模型限制为仅在空间尺度上模拟几个纳米，在时间尺度上模拟几个纳秒。 。为了更全面地研究纳米级磷脂膜的可逆电穿孔机制，并在长达100 ns的较长时间间隔内，我们开发了具有粗粒度马蒂尼力场的二棕榈酰磷脂酰胆碱（DPPC）磷脂膜模型。通过分别检查磷脂膜的形态，亲水通道的大小，膜两侧电压电位的分布以及电穿孔过程中水分子和离子的运动来测试模型。结果结果表明，该过程经历了多个阶段：（1）形成具有表面缺陷的孔。（2）维持毛孔。缺陷扩展到大孔，尺寸保持几纳秒不变。（3）由于自组装导致的毛孔愈合阶段。磷脂膜收缩，孔径减小直到完全封闭。在大多数情况下，孔的横截面不是圆形的，并且在形成孔后，跨膜的电势差急剧降低，即使毛孔开始关闭，也几乎没有恢复膜的完整性。结论粗粒度马蒂尼力场更全面地证明了纳米级可逆电穿孔过程的机理，包括长达100 ns的较长时间范围内的缺陷，膨胀，稳定性和闭孔阶段。考虑必要的分子信息和计算效率。