Voltage imaging reveals the dynamic electrical signatures of human breast cancer cells.
Date
2022-11-11ICR Author
Author
Quicke, P
Sun, Y
Arias-Garcia, M
Beykou, M
Acker, CD
Djamgoz, MBA
Bakal, C
Foust, AJ
Type
Journal Article
Metadata
Show full item recordAbstract
Cancer cells feature a resting membrane potential (Vm) that is depolarized compared to normal cells, and express active ionic conductances, which factor directly in their pathophysiological behavior. Despite similarities to 'excitable' tissues, relatively little is known about cancer cell Vm dynamics. Here high-throughput, cellular-resolution Vm imaging reveals that Vm fluctuates dynamically in several breast cancer cell lines compared to non-cancerous MCF-10A cells. We characterize Vm fluctuations of hundreds of human triple-negative breast cancer MDA-MB-231 cells. By quantifying their Dynamic Electrical Signatures (DESs) through an unsupervised machine-learning protocol, we identify four classes ranging from "noisy" to "blinking/waving". The Vm of MDA-MB-231 cells exhibits spontaneous, transient hyperpolarizations inhibited by the voltage-gated sodium channel blocker tetrodotoxin, and by calcium-activated potassium channel inhibitors apamin and iberiotoxin. The Vm of MCF-10A cells is comparatively static, but fluctuations increase following treatment with transforming growth factor-β1, a canonical inducer of the epithelial-to-mesenchymal transition. These data suggest that the ability to generate Vm fluctuations may be a property of hybrid epithelial-mesenchymal cells or those originated from luminal progenitors.
Collections
Subject
Humans
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Triple Negative Breast Neoplasms
MCF-7 Cells
Membrane Potentials
Research team
Dynamical Cell Systems
Language
eng
Date accepted
2022-10-05
License start date
2022-11-11
Citation
Communications Biology, 2022, 5 (1), pp. 1178 -
Publisher
NATURE PORTFOLIO