Modeling Tumor Treating Fields (TTFields) application in single cells during metaphase and telophase
Abstract
Effects of electric fields on biological cells have been extensively studied but primarily in the low and high frequency regimes. Low frequency AC fields have been investigated for applications to nerve and muscle stimulation or to examine possible environmental effects of 60 Hz excitation. High frequency fields have been studied to understand tissue heating and tumor ablation. Biological effects at intermediate frequencies (in the 100-500 kHz regime) have only recently been discovered and are now being used clinically to disrupt cell division, primarily for the treatment of recurrent glioblastoma multiforme. In this study, we develop a computational framework to investigate the mechanisms of action of these Tumor Treating Fields (TTFields) and to understand in vitro findings observed in cell culture. Using Finite Element Method models of isolated cells we show that the intermediate frequency range is unique because it constitutes a transition region in which the intracellular electric field, shielded at low frequencies, increases significantly. We also show that the threshold at which this increase occurs depends on the dielectric properties of the cell membrane. Furthermore, our models of different stages of the cell cycle and of the morphological changes associated with cytokinesis show that peak dielectrophoretic forces develop within dividing cells exposed to TTFields. These findings are in agreement with in vitro observations, and enhance our understanding of how TTFields disrupt cellular function.
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The DEP force component showed well-defined peak frequencies at 500, 200, and 100 kHz, respectively, for the three stages considered, from the earliest to the latest stage.
“The DEP force component showed well-defined peak frequencies at 500, 200, and 100 kHz, respectively, for the three stages considered, from the earliest to the latest stage [37].”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [37]
The highest maximum intracellular field strength of ~22 V/cm is observed for the cell in late cytokinesis.
“the highest maximum intracellular field strength of ~22 V/cm is observed for the cell in late cytokinesis.”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [37]
The maximum values of the DEP force component decrease with an increasing cell size with equal decay rates for all cytokinesis stages.
“The corresponding maximum values of the DEP force component also decrease with an increasing cell size with equal decay rates for all cytokinesis stages [37].”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [37]
The simulation results predicted that the peak frequencies decrease and converge as a function of an increasing cell radius.
“The simulation results predicted that the above-mentioned peak frequencies decrease and converge as a function of an increasing cell radius.”
From An Overview of Sub-Cellular Mechanisms Involved in the Action of TTFields (2016) · cites this paper as [37]
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REORGANIZAÇÃO ELETROFÍSICA DEPENDENTE DA FREQUÊNCIA EM PHANTOM TUMORAL VASCULARIZADO
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- Authors
- Wenger, C., Giladi, M., Bomzon, Z., Salvador, R., Basser, P. J., & Miranda, P. C.
- Affiliations
- University of Lisbon (PT)
- National Institutes of Health (US)
- Novocure (United States) (US)
- Venue
- 2015 37th Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC)
- Publisher
- IEEE
- Published
- 2015-08
- Volume
- 2015
- Pages
- 6892-6895
- ISSN
- 2375-7477 (ISSN-L)
- OpenAlex
- W2293801493
- Cited by
- 44
- References
- 22
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 2 · 2023: 8 · 2022: 5 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 4 · 2017: 1 · 2016: 5
- FWCI
- 9.09
- Type
- conference paper
- Language
- en
- Open access
- closed
- Locations
- Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- 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 › Cellular Mechanics and Interactions
- Keywords
- tumor treating fields, dielectrophoresis, cell cycle, metaphase, telophase, cytokinesis, glioblastoma
- MeSH terms
- Electricity, Electric Stimulation Therapy, Humans, Metaphase, Spindle Apparatus, Models, Theoretical, Neoplasms, Telophase, Cell Line, Tumor
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