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.
Tumor treating fields (TTF) therapy is an innovative tumor treatment modality. Currently, the TTF devices predominantly employ insulated ceramic electrodes as the electric field transmission medium, resulting in low energy transfer efficiency of the electric field and poor portability of the devices. This study proposed an innovative TTF transmission mode and independently designed a conducted-electrode TTF cell culture dish utilizing inert titanium materials. The electric field conduction characteristics were verified through finite element simulations and experimental tests. Finally, based on the self-manufactured conducted-electrode TTF cell culture dish, experiments on the proliferation inhibition of U87 tumor cells by TTF were conducted. The results demonstrated that under an applied TTF voltage of 10 V and frequency of 200 kHz, the electric field intensities within the medium for conducted and insulated electrodes are approximately 2.5 V/cm and 0.7 V/cm, respectively. Compared to conventional insulated TTF systems, the conducted-electrode TTF configuration exhibited a lower electrode voltage drop and a higher electric field intensity in the culture medium, indicating superior electric field transmission efficiency. Following 36 hours of treatment with conducted-electrode TTF on U87 cells, the proliferation inhibition rate reached approximately 50%, demonstrating effective suppression of tumor cell growth. This approach presents a potential direction for optimizing TTF treatment modality and device design.