## 4 Discussion
The relationship between the discharging time (which equals \(5T_{cell}\)) and the local dynamic conductivity of the cell membrane was proposed in [55]. The local dynamic conductivity varies at different locations of the cell membrane (see Figure 4b), which leads to different discharging times at different locations. It is interesting to mention that the discharging time in the polar region is the shortest, which explains why pores in this region are unable to grow. In addition, the effective membrane tension \(\sigma_{eff}\) also plays a significant role in the rate of pore size change. The \(\sigma_{eff}\) is a positive source for pore expansion. However, the increasing overall pore area will lead to a decrease in the \(\sigma_{eff}\), which adversely hinders pores from growing. This closed loop explains why all pulsing protocols have an approximate plateau of PAR. Besides, given that the proportion of PAR is limited, those pores with less energy to grow will fail in competition with more energetic pores, and consequently, more PAR is gradually allocated to those energetic pores, allowing them to become larger. That is the reason why the transition region constantly shrinks over time. The SCE model is a widely recognized principle-based modeling approach in the field of electroporation. It is built on the transient aqueous pore theory [56; 57], which posits that pores initially appear in a hydrophobic state and spontaneously transition to a hydrophilic state when they exceed a certain free energy threshold. The process of pore evolution during electroporation is consistent with results observed in the molecular dynamics simulations [32; 58]. Over the years, the SCE model has become a powerful tool for understanding and predicting the evolution of pores during electroporation-based applications. It can effectively reflect the dynamics of electroporation at the scale of a single cell or multiple cells over a period of several minutes to hours. On the other hand, molecular dynamics techniques provide a more detailed understanding at the molecular scale but require a significant amount of computational power and time and, consequently, can only simulate a small portion of the cell membrane. To predict the ablation zone of electroporation, numerical models based on the electric field distribution are the prevailing method. With a lethal threshold determined through experiments, the electric field distribution of a given scenario can be used to predict the ablation zone [59; 60]. Some derivative modeling methods have been developed to improve the effectiveness of this electric field distribution-based approach [19; 61; 62]. However, all relevant methods are inevitably dependent on the experimental data, making them semi-empirical in nature. In general, there are three main modeling methods in electroporation. The smaller scale a method can simulate, the more detailed insights it can provide. From the perspective of determining pulse-setting parameters, the SCE model is a suitable choice as it incorporates the principles behind electroporation and can simulate the process of electroporation at the cellular scale. Early studies were dedicated to understanding the principles behind the SCE model, with one notable example being [28]. Since then, researchers have focused on exploring the potential of the SCE model in various applications. For instance, [PERSON] et al. [30] applied it to irregular cell shapes, [PERSON] et al. [34] utilized it to explore sinusoidal pulses, and [PERSON] et al. [37] employed it to evaluate the role of duty cycle and interval in H-FIRE protocols. [PERSON] et al. [63] expanded its applicability to nanosecond pulses by introducing dielectric dispersion. [PERSON] et al. [64] and [PERSON] et al. [36] deepened the exploration of nanosecond pulses. In the field of tumor ablation, the likelihood of cell death is of particular interest, such that understanding the relationship between the probability of cell death and the dynamics of electroporation is crucial, which is yet poorly understood.