Dielectrophoresis as a Tool to Reveal the Potential Role of Ion Channels and Early Electrophysiological Changes in Osteoarthritis

Abstract

Diseases such as osteoarthritis (OA) are commonly characterized at the molecular scale by gene expression and subsequent protein production; likewise, the effects of pharmaceutical interventions are typically characterized by the effects of molecular interactions. However, these phenomena are usually preceded by numerous precursor steps, many of which involve significant ion influx or efflux. As a consequence, rapid assessment of cell electrophysiology could play a significant role in unravelling the mechanisms underlying drug interactions and progression of diseases, such as OA. In this study, we used dielectrophoresis (DEP), a technique that allows rapid, label-free determination of the dielectric parameters to assess the role of potassium ions on the dielectric characteristics of chondrocytes, and to investigate the electrophysiological differences between healthy chondrocytes and those from an in vitro arthritic disease model. Our results showed that DEP was able to detect a significant decrease in membrane conductance (6191 ± 738 vs. 8571 ± 1010 S/m2), membrane capacitance (10.3 ± 1.47 vs. 14.5 ± 0.01 mF/m2), and whole cell capacitance (5.4 ± 0.7 vs. 7.5 ± 0.3 pF) following inhibition of potassium channels using 10 mM tetraethyl ammonium, compared to untreated healthy chondrocytes. Moreover, cells from the OA model had a different response to DEP force in comparison to healthy cells; this was seen in terms of both a decreased membrane conductivity (782 S/m2 vs. 1139 S/m2) and a higher whole cell capacitance (9.58 ± 3.4 vs. 3.7 ± 1.3 pF). The results show that DEP offers a high throughput method, capable of detecting changes in membrane electrophysiological properties and differences between disease states.

A Magnetically and Electrically Powered Hybrid Micromotor in Conductive Solutions: Synergistic Propulsion Effects and Label‐Free Cargo Transport and Sensing

“…Apoptotic status can be analyzed or excluded for analysis in the single-cell samples from drug discovery, developing of cell therapeutics and monitoring response in an immunotherapy. Moreover, dielectrophoresis can be used to reveal the membrane potential of biological changes of membrane [65] of a single cell or organelle (e.g., mitochondria). [66] In our recent publication [67] using low-conductivity solutions for better electric propulsion, an intact mammalian cell (K562) was not manipulable by the JP due to its pDEP characteristics, which led to its electroporation upon contact with localized high electric field regions on the JP surface.…”

“…Apoptotic status can be analyzed or excluded for analysis in the single‐cell samples from drug discovery, developing of cell therapeutics and monitoring response in an immunotherapy. Moreover, dielectrophoresis can be used to reveal the membrane potential of biological changes of membrane [ 65 ] of a single cell or organelle (e.g., mitochondria). [ 66 ]…”