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Cited by 59Electromagnetic Fields and Biological EffectsMicrobial Inactivation MethodsMicrotubule and mitosis dynamics

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

Li, Xing, Yang, Fan, Rubinsky, Boris·2020·IEEE Transactions on Biomedical Engineering
DOI 10.1109/tbme.2020.2965883
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Abstract

OBJECTIVE: A theoretical study on the mechanisms through which Tumor Treating Fields (TTFields) affect dividing tumor cells. METHODS: Numerical analysis was used to revisit two previously proposed mechanisms and introduce a third. We examine the previous hypotheses that: a) TTFields generate a moment that affects microtubule assembly during early mitosis, and b) dielectrophoretic (DEP) forces cause neutral particles to move toward the cleavage furrow during the telophase stage. We further introduce a new hypothesis that TTFields modify cell membrane potential in dividing tumor cells. RESULTS: a) The Brownian energy is several orders of magnitude larger than the moment induced by TTFields on tubulin dimers. b) Adding Stokes drag forces to DEP forces shows that the motion of the particles in the cytoplasm is very slow, approximately 0.003 µm/s, and therefore, unless the duration of the telophase is long enough there will be no substantial effect from the DEP forces. c) The Schwan equation shows that electric fields at the frequencies of clinical TTFields can cause a 10%-17% change in tumor cell membrane potential. CONCLUSION: Our studies find limited support for the previously suggested hypotheses and suggest that the TTFields affect ion channels by inducing cell membrane potential change could be a mechanism of tumor cell death. SIGNIFICANCE: Previously suggested mechanisms of tumor cell death from TTFields are found lacking. The effect of TTFields on the tumor cell membrane potential warrants further research.

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Crossref · 10.1109/tbme.2020.2965883

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35 of 35 references verified0 citation errors · 0 not checkable

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  • The Vm of both non-cancer and cancer cells depolarizes during proliferation to about −15 mV, but post-mitotic non-cancer cells return to a typical resting Vm of −70 mV whereas post-mitotic cancer cells achieve a resting Vm of −25 mV.

    “The Vm of both non-cancer and cancer cells depolarizes during proliferation, to about −15 mV, but post-mitotic non-cancer cells return to a typical resting Vm of −70 mV whereas post-mitotic cancer cells achieve a resting Vm of −25 mV [51,69].”

    From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [69]

  • Modeling studies suggest that the magnitude of the electric field caused by TTFields may not be sufficient to overcome Brownian motion inherent within the cytoplasm of single cancer cells.

    “In addition, recent modeling studies in the context of dipole alignment suggest that the magnitude of the electric field caused by TTFields may not be sufficient to overcome Brownian motion inherent within the cytoplasm of single cancer cells [51,69].”

    From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [69]

  • The relatively depolarized resting Vm in cancer cells could explain why, compared to non-cancer cells, cancer cells are more vulnerable to both electroporation and TTFields.

    “The relatively depolarized resting Vm in cancer cells [28,29,30,31,73,74,75] could explain why, compared to non-cancer cells, cancer cells are more vulnerable to both electroporation and TTFields [67,69] (see Table S4).”

    From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [69]

  • The membrane potential could serve as an important read-out to monitor in studies of TTFields.

    “Certainly, the recent work of Li et al. [51,69] suggests that the membrane potential could serve as an important read-out to monitor in studies of TTFields.”

    From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [69]

  • Finite element modeling predicts that when cells are in close proximity, electric field lines are concentrated between contact points in a frequency-dependent manner.

    “Indeed, research by some of us (co-authors TM and ZB, personal communication) shows that finite element modeling predicts that when cells are in close proximity to each other, electric field lines are concentrated between the contact points in a frequency-dependent manner [51,69].”

    From Permeabilizing Cell Membranes with Electric Fields (2021) · cites this paper as [69]

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Authors
Li, X., Yang, F., & Rubinsky, B.
Affiliations
  • Chongqing University (CN)
  • University of California, Berkeley (US)
ORCID
Venue
IEEE Transactions on Biomedical Engineering
Publisher
Institute of Electrical and Electronics Engineers (IEEE)
Published
2020-09
Volume
67
Issue
9
Pages
2594-2602
ISSN
  • 0018-9294 (ISSN-L)
  • 1558-2531
DOI
10.1109/tbme.2020.2965883
OpenAlex
W2999190353
Cited by
59
References
36
Citations by year
2026: 5 · 2025: 7 · 2024: 10 · 2023: 13 · 2022: 12 · 2021: 8 · 2020: 4
FWCI
4.41
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • IEEE Transactions on Biomedical Engineering (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Higher Education Discipline Innovation Project (B08036)
  • CSC scholarship
  • National Natural Science Foundation of China (51777023)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Electromagnetic Fields and Biological Effects
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Microbial Inactivation Methods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
Keywords
tumor treating fields, mitosis, cancer cell death, microtubule assembly, dielectrophoresis, membrane potential, ion channels, Stokes drag, Brownian motion, tubulin dimers, electric field effects, cleavage furrow
MeSH terms
Electricity, Electric Stimulation Therapy, Humans, Mitosis, Models, Theoretical, Neoplasms

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