Li Xing, Liu Kaida, Guo Cong, Fang Tianrui, Yang Fan
College of Automation Engineering, Nanjing University of Aeronautics and Astronautics, Nan Jing 210016, P. R. China.
School of Electrical Engineering, Chongqing University, Chongqing 400044, P. R. China.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2024 Jun 25;41(3):569-576. doi: 10.7507/1001-5515.202312063.
Tumor treatment fields (TTFields) can effectively inhibit the proliferation of tumor cells, but its mechanism remains exclusive. The destruction of cellular microtubule structure caused by TTFields through electric field force is considered to be the main reason for inhibiting tumor cell proliferation. However, the validity of this hypothesis still lacks exploration at the mesoscopic level. Therefore, in this study, we built force models for tubulins subjected to TTFields, based on the physical and electrical properties of tubulin molecules. We theoretically analyzed and simulated the dynamic effects of electric field force and torque on tubulin monomer polymerization, as well as the alignment and orientation of α/β tubulin heterodimer, respectively. Research results indicate that the interference of electric field force induced by TTFields on tubulin monomer is notably weaker than the inherent electrostatic binding force among tubulin monomers. Additionally, the electric field torque generated by the TTFileds on α/β tubulin dimers is also difficult to affect their random alignment. Therefore, at the mesoscale, our study affirms that TTFields are improbable to destabilize cellular microtubule structures via electric field dynamics effects. These results challenge the traditional view that TTFields destroy the microtubule structure of cells through TTFields electric field force, and proposes a new approach that should pay more attention to the "non-mechanical" effects of TTFields in the study of TTFields mechanism. This study can provide reliable theoretical basis and inspire new research directions for revealing the mesoscopic bioelectrical mechanism of TTFields.
肿瘤治疗电场(TTFields)能够有效抑制肿瘤细胞增殖,但其机制尚不明确。TTFields通过电场力导致细胞微管结构破坏被认为是抑制肿瘤细胞增殖的主要原因。然而,这一假说的正确性在介观层面仍缺乏探索。因此,在本研究中,我们基于微管蛋白分子的物理和电学性质,构建了受TTFields作用的微管蛋白受力模型。我们分别从理论上分析并模拟了电场力和扭矩对微管蛋白单体聚合以及α/β微管蛋白异二聚体排列和取向的动态影响。研究结果表明,TTFields诱导的电场力对微管蛋白单体的干扰明显弱于微管蛋白单体之间固有的静电结合力。此外,TTFields对α/β微管蛋白二聚体产生的电场扭矩也难以影响其随机排列。因此,在介观尺度上,我们的研究证实TTFields不太可能通过电场动力学效应破坏细胞微管结构。这些结果挑战了传统观点,即TTFields通过电场力破坏细胞的微管结构,并提出了一种新的途径,即在TTFields机制研究中应更多关注TTFields的“非机械”效应。本研究可为揭示TTFields的介观生物电机制提供可靠的理论依据,并启发新的研究方向。
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