Abstract
Long-standing research on electric and electromagnetic field interactions with biological cells and their subcellular structures has mainly focused on the low- and high-frequency regimes. Biological effects at intermediate frequencies between 100 and 300 kHz have been recently discovered and applied to cancer cells as a therapeutic modality called Tumor Treating Fields (TTFields). TTFields are clinically applied to disrupt cell division, primarily for the treatment of glioblastoma multiforme (GBM). In this review, we provide an assessment of possible physical interactions between 100 kHz range alternating electric fields and biological cells in general and their nano-scale subcellular structures in particular. This is intended to mechanistically elucidate the observed strong disruptive effects in cancer cells. Computational models of isolated cells subject to TTFields predict that for intermediate frequencies the intracellular electric field strength significantly increases and that peak dielectrophoretic forces develop in dividing cells. These findings are in agreement with in vitro observations of TTFields’ disruptive effects on cellular function. We conclude that the most likely candidates to provide a quantitative explanation of these effects are ionic condensation waves around microtubules as well as dielectrophoretic effects on the dipole moments of microtubules. A less likely possibility is the involvement of actin filaments or ion channels.
Highlights
The effects of external electric fields on biological cells have been extensively studied both in the direct current (DC) and alternating current (AC) cases [1]
Owing to the fact that there have been many previous reviews of electromagnetic effects in biology [1,56,57,58], here we mainly focus on the electrical properties of MTs, actin actin filaments (AFs), ion channels, cytoplasmic ions and DNA with special interest into dynamical electrical properties involving AC
Calculating the force due to an electric field of a static electric field with a strength of 1 V/cm acting on a 10 μm-long microtubule, we find from F = qE, with q = 10−13 C for unscreened charges, that results in F = 10 pN assuming the field is largely undiminished when penetrating a cell, which is in general a major oversimplification
Summary
The effects of external electric fields on biological cells have been extensively studied both in the direct current (DC) and alternating current (AC) cases [1]. Reported the discovery that low-intensity (1–3 V/cm), intermediate frequency (100–300 kHz) electric fields have a profoundly inhibitory effect on the growth rate of various mammalian tumor cell lines [2,3,4] This discovery has been translated into a clinical application termed Tumor Treating. A significant prolongation of mitosis was predicted, where treated cells remain stationary at metaphase for several hours, which was accompanied by abnormal mitotic figures as well as membrane rupture and blebbing leading to apoptosis [2,3] These experiments showed that the inhibitory effect increases with an increasing electric field intensity, resulting in a complete proliferation arrest of rat glioma cells after 24 h exposure to a field intensity of.
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