肿瘤治疗电场对细胞微管蛋白的介观动力学影响研究
Study on the mesoscopic dynamic effects of tumor treating fields on cell tubulin
李星 1刘开达 1郭琮 1房天瑞 1杨帆2
作者信息
- 1. 南京航空航天大学 自动化学院(南京 210016)
- 2. 重庆大学 电气工程学院(重庆 400044)
- 折叠
摘要
肿瘤治疗电场(TTFields)对肿瘤细胞增殖具有抑制效应,但其抑制机制尚不明晰.TTFields通过电场力破坏细胞微管结构被认为是抑制肿瘤细胞增殖的主要原因,然而这一猜想成立与否还缺乏介观层面的探究.因此,本文基于细胞微管蛋白的物理结构和电学特性,建立肿瘤细胞微管蛋白在TTFields电场作用下的受力模型,通过理论和仿真分析电场力、力矩分别对微管蛋白单体聚合及α/β异二聚体微管蛋白排列取向的动力学影响.研究结果表明,TTFields对微管蛋白单体的电场力远小于微管蛋白单体之间的静电聚合力,对α/β异二聚体微管蛋白所产生的力矩也难以影响其随机排列取向,进而在介观尺度上,证明了 TTFields难以通过电场力学效应破坏细胞微管结构的稳定性.该结果对TTFields通过电场力破坏细胞微管结构这一传统观点表示质疑,并提出在TTFields机制研究中应当更加关注TTFields"非力"效应的新思路.本文的研究可为TTFields的介观生物电学机制揭示提供可靠的理论依据和激发新的研究方向.
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.
关键词
肿瘤治疗电场/微管蛋白/动力学效应/介观机制Key words
Tumor treatment fields/Tubulin/Dynamics effects/Mesoscopic mechanism引用本文复制引用
基金项目
科技部外国专家项目(G2023181006L)
江苏省创新训练项目(202310287127Y)
出版年
2024
NETL
NSTL
万方数据