Comprehensive simulations of intracellular electric fields during exposure to tumor treating fields

Electric fields, as a unique physical form, have been widely used to manipulate and modulate biological processes. Tumor treating fields (TTFields) is one of the electro-therapy methods that deliveries intermediate frequency (100 kHz - 300 kHz), low intensity (1 V/cm - 3 V/cm) sinusoidal alternating current (AC) electric fields to inhibit tumor cell growth. When the tumor cells are exposed to TTFields, intracellular electric fields distribution will be a crucial clue for evaluating therapeutic effects and revealing mechanisms. This work systematically studied the TTFields distribution penetrating into the tumor cells by finite element method (FEM) simulations. We analyzed and compared the effects of various variables on the intracellular electric fields, including TTFields parameters, cellular geometry, and cellular electrical properties. We found that TTFields frequency, cell radius, cell membrane permittivity, cytoplasmic conductivity have significant impacts on the strength of intracellular electric fields. The results can be helpful for revealing TTFields mechanisms, explaining optimal parameter selection and better TTFields protocol design for different tumor types.