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Biology subjects

Moreddu, R.

Publications and source records attributed to Moreddu, R..

3 recordsLinked to original sources

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.

bioengineering↗

An agent-based 3D model of non-genetic adaptation in cancer tissues under electrical, mechanical, and hypoxic stress

Non-genetic adaptation enables cancer cells to alter their phenotype under stress without requiring new mutations. However, the mechanisms by which electrical, mechanical, and hypoxic cues combine to shape this process in 3D tissues remain poorly understood. This work presents an agent-based tumor model that integrates vascular oxygen supply, a globally imposed electric field, mechanically mediated crowding and compression cues, phenotype transitions, cell growth, mitosis, death, and inheritance of adaptive memory across division. The simulated tumors exhibit a three-stage trajectory consisting of necrosis onset, transient collapse of live mass, and partial regrowth accompanied by progressive accumulation of adapted cells. Continuous electrical stimulation produces a dose-dependent reduction in live mass while markedly increasing the adapted fraction, with comparatively limited changes in final necrotic burden. This response is strongly conditioned by mechanics and reshapes (and is reshaped by) adaptive capacity. Pulsed stimulation further shows that, in the model, electric field amplitude and temporal schedule jointly determine memory phenomena, phenotypic diversification, and growth recovery. These results show that coupling local oxygen availability, mechanical constraints, electrical forcing, and history-dependent phenotype transitions can generate distinct tissue-level patterns of phenotypic heterogeneity. Both stimulus magnitude and temporal protocol influenced the resulting population structure, suggesting that the history of physical stress may be an important determinant of adaptive dynamics in spatially organized tumor models.

biophysics↗

High-frequency extracellular spiking in electrically-active cancer cells

Microelectrode matrices have been extensively used in the past 30 years as a reliable platform to record the extracellular activity of cells traditionally regarded to as excitable, i.e. brain cells and muscle cells. Meanwhile, fundamental biology studies on cancer cells since the 1970s reveal that they exhibit altered functionalities of ion channels, membrane potentials, metabolism, and communication mechanisms when compared to their healthy counterparts. In this work, we present for the first time the presence of extracellular voltage spikes occurring at high frequencies (0.1-3.5 kHz) in breast cancer cells, resembling the ones observed in excitable cells, and the possibility to record them with 30 {micro}m TiN microelectrode matrices. These preliminary findings may open a new path for exploration in a variety of research fields, enabling the access to bioelectrical dynamics in cancer cells and cell networks, targeting bioelectricity as a tool in anticancer drug development and cancer diagnostics, as well as provide a market expansion for companies commercializing microelectrodes and microelectrode recording systems.

bioengineering↗