Abstract 5228: The impact of microtubules on solution conductance and capacitance; implications for the use of AC electric fields in cancer therapy
Authors: Tuszynski Jack A. , Santelices Iara , Friesen Douglas E. , Bell Clayton , Xiao Jack , Rezania Vahid , Freedman Holly , Hough Cameron , Tsung Andrew J. , Velpula Kiran K. , Shankar Karthik 
Published: July 2017

Microtubules (MTs) form mitotic spindles in dividing cells but have also been implicated in electrical signaling in biology, and may act as biological nanowires. Importantly, relatively weak AC electric fields with frequencies between 100-300 kHz and strengths in the range ~1-2.5 V/cm, called Tumor Treating Fields (TTFields), have been shown to arrest cancer cells’ mitosis and have led to an FDA approved treatment of glioblastoma multiforme. TTFields’ effect on MTs has motivated our study of their electrical properties. Here, we designed two platinum electrodes 14 μm apart and performed electrical characterization of solutions with various concentrations of MTs, tubulin dimers and ions, at a range of AC frequencies between 1 kHz and 1 MHz to uncover an optimal protocol to quantify MT electrical effects in vitro. We generated a theoretical basis for the results observed, by analyzing the response of ions as the principal charge carriers attracted to MTs and tubulin. We observed that MTs measurably increase the solution’s conductance, and this effect is more pronounced at lower ionic concentrations. We model the possibility that this effect is due to a larger percentage of ions being able to use MTs as low-resistance cables. The intrinsic conductivity of MTs has been found to be two orders of magnitude greater than that of the buffer solution. Moreover, we found that at 100 kHz the conductance of MTs reaches its peak. On the other hand, at low protein concentration, free tubulin dimers decrease solution’s conductance, and we model this as being due to tubulin attracting ionic charges and lowering their mobility. Both tubulin and MTs were found to increase capacitance of buffer solutions, due to their formation of ionic double layers. These results point to MTs being very sensitive to AC electric fields and further support their electrical signaling, an emerging property in biological organization. Modulating electrical signaling via 100kHz fields may impact intra-cellular communication as well as organization of the cytoskeleton. These results bring insight into MTs ability to modulate the capacitance and conductance of the cytoplasm and act as low resistance pathways for ions, which has implications for understanding of the action of TTFields on cancer cells.

Citation Format: Jack A. Tuszynski, Iara Santelices, Douglas E. Friesen, Clayton Bell, Jack Xiao, Vahid Rezania, Holly Freedman, Cameron Hough, Andrew J. Tsung, Kiran K. Velpula, Karthik Shankar. The impact of microtubules on solution conductance and capacitance; implications for the use of AC electric fields in cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5228. doi:10.1158/1538-7445.AM2017-5228