Modeling Tumor Treating Fields (TTFields) application in single cells during metaphase and telophase

Area of Science:

• Biophysics
• Computational Biology
• Oncology

Background:

• Electric field effects on cells are known at low (stimulation) and high (heating) frequencies.
• Intermediate frequency electric fields (100-500 kHz) show novel biological effects, clinically used for cancer treatment.
• Tumor Treating Fields (TTFields) are a recent therapeutic modality for recurrent glioblastoma multiforme.

Purpose of the Study:

• To develop a computational framework for investigating Tumor Treating Fields (TTFields) mechanisms.
• To understand in vitro findings related to TTFields' effects on cell division.
• To elucidate the biophysical principles underlying TTFields' efficacy.

Main Methods:

• Utilized Finite Element Method (FEM) modeling of isolated cells.
• Simulated cells across different stages of the cell cycle and during cytokinesis.
• Analyzed the impact of intermediate frequency electric fields on intracellular electric field strength and dielectrophoretic forces.

Main Results:

• Demonstrated that intermediate frequencies represent a transition zone where intracellular electric fields increase significantly, unlike low frequencies.
• Showed that the threshold for this intracellular field increase is dependent on cell membrane dielectric properties.
• Identified peak dielectrophoretic forces in dividing cells exposed to TTFields, particularly during cytokinesis.

Conclusions:

• The computational framework successfully explains in vitro observations of TTFields' effects.
• Intermediate frequency electric fields have unique biophysical interactions with cells, especially dividing ones.
• TTFields disrupt cellular function by generating significant dielectrophoretic forces during cell division.