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[肿瘤治疗电场对细胞微管蛋白的介观动力学效应研究]

[Study on the mesoscopic dynamic effects of tumor treating fields on cell tubulin].

作者信息

Li Xing, Liu Kaida, Guo Cong, Fang Tianrui, Yang Fan

机构信息

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.

出版信息

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2024 Jun 25;41(3):569-576. doi: 10.7507/1001-5515.202312063.


DOI:10.7507/1001-5515.202312063
PMID:38932544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11208644/
Abstract

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.

摘要

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。

相似文献

[1]
[Study on the mesoscopic dynamic effects of tumor treating fields on cell tubulin].

Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2024-6-25

[2]
Electrodynamic interaction between tumor treating fields and microtubule electrophysiological activities.

APL Bioeng. 2024-6-3

[3]
Tumor Treating Fields (TTFields) Hinder Cancer Cell Motility through Regulation of Microtubule and Acting Dynamics.

Cancers (Basel). 2020-10-17

[4]
A Theoretical Study on the Biophysical Mechanisms by Which Tumor Treating Fields Affect Tumor Cells During Mitosis.

IEEE Trans Biomed Eng. 2020-9

[5]
Mitotic Spindle Disruption by Alternating Electric Fields Leads to Improper Chromosome Segregation and Mitotic Catastrophe in Cancer Cells.

Sci Rep. 2015-12-11

[6]
A Comprehensive Study on the Electrostatic Properties of Tubulin-Tubulin Complexes in Microtubules.

Cells. 2023-1-5

[7]
The dielectric properties of skin and their influence on the delivery of tumor treating fields to the torso: a study combining in vivo measurements with numerical simulations.

Phys Med Biol. 2019-9-19

[8]
A Theoretical Analysis of the Effects of Tumor-Treating Electric Fields on Single Cells.

Bioelectromagnetics. 2020-9

[9]
The schemes, mechanisms and molecular pathway changes of Tumor Treating Fields (TTFields) alone or in combination with radiotherapy and chemotherapy.

Cell Death Discov. 2022-10-11

[10]
An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields.

Int J Environ Res Public Health. 2016-11-12

引用本文的文献

[1]
Advancement in tumor treating fields of mechanism, clinical applications, and future directions.

Discov Oncol. 2025-6-10

本文引用的文献

[1]
A Comprehensive Study on the Electrostatic Properties of Tubulin-Tubulin Complexes in Microtubules.

Cells. 2023-1-5

[2]
Nanoscale Viscosity of Cytoplasm Is Conserved in Human Cell Lines.

J Phys Chem Lett. 2020-8-20

[3]
Mechanisms of microtubule dynamics and force generation examined with computational modeling and electron cryotomography.

Nat Commun. 2020-7-28

[4]
A Theoretical Study on the Biophysical Mechanisms by Which Tumor Treating Fields Affect Tumor Cells During Mitosis.

IEEE Trans Biomed Eng. 2020-9

[5]
Tumour Treating Fields in combination with pemetrexed and cisplatin or carboplatin as first-line treatment for unresectable malignant pleural mesothelioma (STELLAR): a multicentre, single-arm phase 2 trial.

Lancet Oncol. 2019-10-15

[6]
Tumor-Treating Fields: A Fourth Modality in Cancer Treatment.

Clin Cancer Res. 2017-8-1

[7]
Tumor treating fields: a novel treatment modality and its use in brain tumors.

Neuro Oncol. 2016-10

[8]
External electric field effects on the mechanical properties of the αβ-tubulin dimer of microtubules: a molecular dynamics study.

J Mol Model. 2014-8

[9]
Electrophoresis of individual microtubules in microchannels.

Proc Natl Acad Sci U S A. 2007-5-8

[10]
Dielectric measurement of individual microtubules using the electroorientation method.

Biophys J. 2006-5-15

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