Substrate chemistry in cancer bioelectronics: phenotype-dependent cell-electrode coupling and motility

Electrode coatings are routinely applied to promote cell attachment in bioelectronics, yet their influence on what the electrode reports is less examined. This is particularly relevant for cell types whose electrical signatures are yet to be fully understood and where coating selection is largely inherited from neuroscience. Here, we compare three breast epithelial phenotypes of increasing invasiveness on interdigitated gold microelectrodes carrying six surface chemistries: uncoated gold, poly-L-lysine (PLL), fibronectin, laminin, and PLL under-layered with each protein (PLL+F, PLL+L). Continuous impedance recording at 1 kHz and 41.5 kHz over the first 17 h, spatial impedance mapping at 24 h, 50 h migration assays and single-cell trajectory analysis were used to evaluate cell-electrode coupling and relate it to motility in the two extremes of the spectrum. Each cell line produced its electrical and migratory signature, and the effect of coating depended on phenotype. Initial coupling and motility were found to be inversely related in the invasive line and unrelated in the non-tumorigenic one. We conclude that the electrode coating is an experimental variable that interacts with phenotype and carries its own electrical signature, and the choice of coating must be driven, beyond physiological relevance, by the requirement for adherent vs. motile cells.