Department of Bioengineering and California Institute for Quantitative Biosciences (QB3), University of California, Berkeley, CA 94720, USA; Department of Material Science and Engineering, University of California, Berkeley, CA 94720, USA.
Department of Biomedical Engineering and Mechanics, Virginia Tech, Blacksburg, VA 24061, USA.
Bioelectrochemistry. 2021 Aug;140:107800. doi: 10.1016/j.bioelechem.2021.107800. Epub 2021 Apr 20.
Experimental evidence has demonstrated the ability of transient pulses of electric fields to alter mammalian cell behavior. Strategies with these pulsed electric fields (PEFs) have been developed for clinical applications in cancer therapeutics, in-vivo decellularization, and tissue regeneration. Successful implementation of these strategies involve understanding how PEFs impact the cellular structures and, hence, cell behavior. The caveat, however, is that the PEF parameter space (i.e., comprising different pulse widths, amplitudes, number of pulses) is large, and design of experiments to explore all possible combinations of pulse parameters is prohibitive from a cost and time standpoint. In this study, a scaling law based on the Ising model is introduced to understand the impact of PEFs on the outer cell lipid membrane so that an understanding developed in one PEF pulse regime may be extended to another. Combining non-Markovian Monte Carlo techniques to determine density-of-states with a novel non-equilibrium thermodynamic framework based on the principle of steepest entropy ascent, the applicability of this scaling model to predict the behavior of both thermally quenched and electrically perturbed lipid membranes is demonstrated. A comparison of the predictions made by the steepest-entropy-ascent quantum thermodynamic (SEAQT) framework to experimental data is performed to validate the robustness of this computational methodology and the resulting scaling law.
实验证据表明，瞬时电场脉冲能够改变哺乳动物细胞的行为。这些脉冲电场 (PEF) 的策略已经被开发用于癌症治疗、体内去细胞化和组织再生的临床应用。成功实施这些策略需要了解 PEF 如何影响细胞结构，从而影响细胞行为。然而，需要注意的是，PEF 参数空间（即包含不同的脉冲宽度、幅度、脉冲数量）很大，从成本和时间的角度来看，设计实验来探索所有可能的脉冲参数组合是不可行的。在这项研究中，引入了一种基于伊辛模型的标度定律来理解 PEF 对细胞外脂质膜的影响，以便在一个 PEF 脉冲状态下获得的理解可以扩展到另一个状态。通过将非马尔可夫蒙特卡罗技术与基于最陡熵上升原理的新型非平衡热力学框架相结合来确定态密度，证明了该标度模型在预测热淬火和电扰动脂质膜行为方面的适用性。通过将最陡熵上升量子热力学 (SEAQT) 框架的预测与实验数据进行比较，验证了这种计算方法的稳健性和由此产生的标度律。
