Human Breast Cancer Cells Demonstrate Electrical Excitability

Abstract

Breast cancer is one of the most prevalent types of cancers worldwide and yet, its pathophysiology is poorly understood. Single-cell electrophysiological studies have provided evidence that membrane depolarization is implicated in the proliferation and metastasis of breast cancer. However, metastatic breast cancer cells are highly dynamic microscopic systems with complexities beyond a single-cell level. There is an urgent need for electrophysiological studies and technologies capable of decoding the intercellular signaling pathways and networks that control proliferation and metastasis, particularly at a population level. Hence, we present for the first time non-invasive in vitro electrical recordings of strongly metastatic MDA-MB-231 and weakly/non-metastatic MCF-7 breast cancer cell lines. To accomplish this, we fabricated an ultra-low noise sensor that exploits large-area electrodes, of 2 mm 2 , which maximizes the double-layer capacitance and concomitant detection sensitivity. We show that the current recorded after adherence of the cells is dominated by the opening of voltage-gated sodium channels (VGSCs), confirmed by application of the highly specific inhibitor, tetrodotoxin (TTX). The electrical activity of MDA-MB-231 cells surpasses that of the MCF-7 cells, suggesting a link between the cells' bioelectricity and invasiveness. We also recorded an activity pattern with characteristics similar to that of Random Telegraph Signal (RTS) noise. RTS patterns were less frequent than the asynchronous VGSC signals. The RTS noise power spectral density showed a Lorentzian shape, which revealed the presence of a low-frequency signal across MDA-MB-231 cell populations with propagation speeds of the same order as those reported for intercellular Ca 2+ waves. Our recording platform paves the way for real-time investigations of the bioelectricity of cancer cells, their ionic/pharmacological properties and relationship to metastatic potential.

Impedimetric Characterization of Bioelectronic Nano-Antennae

“…as expected due to the low concentration of ions; values are reasonable as the dH2O resistance is rated at 18.2 MΩ.cm and there is a 1 mm gap between electrodes. PBS impedance is in the order of kΩ, also reasonable for this concentration (Ribeiro et al, 2020). The results presented…”

Toward Hijacking Bioelectricity in Cancer to Develop New Bioelectronic Medicine

“…For instance, multi‐electrode arrays detected a higher electrical activity of metastatic versus non‐metastatic breast cancer cells associated with a higher activity of VGSCs. [ 102 ] Fluorescence reporters have also been suggested for bioelectricity measurements due to their inherent advantage of high resolution, simplistic in vivo analysis, and ability to track bioelectric gradients over long periods even with ongoing cellular activities. [ 103 ] A vibrating probe made up of an insulated, sharpened metal wire with a small platinum‐black tip has been used to non‐invasively measure the bioelectric current (μA cm −2 range) near cells and tissues in physiological media.…”

A bioelectric model of carcinogenesis, including propagation of cell membrane depolarization and reversal therapies

“…Also very relevant are the community effects associated with cell electrical communication, leading to both short and long range influence and patterns 42 , and their importance in cancer, as the link between the cells’ bioelectric state and invasiveness 49 or the role signaling by calcium permeable channels play in tumor progress 50 . The manipulation of the tissue bioelectric state, profiting from the long range impact and propagation of the polarization state, can be an effective and efficient approach for cancer prevention and therapy.…”