Broadband Electrical Spectroscopy to Distinguish Single-Cell Ca(2+) Changes Due to Ionomycin Treatment in a Skeletal Muscle Cell Line

Many skeletal muscle diseases such as muscular dystrophy, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and sarcopenia share the dysregulation of calcium (Ca(2+)) as a key mechanism of disease at a cellular level. Cytosolic concentrations of Ca(2+) can signal dysregulation in organelles including the mitochondria, nucleus, and sarcoplasmic reticulum in skeletal muscle. In this work, a treatment is applied to mimic the Ca(2+) increase associated with these atrophy-related disease states, and broadband impedance measurements are taken for single cells with and without this treatment using a microfluidic device. The resulting impedance measurements are fitted using a single-shell circuit simulation to show calculated electrical dielectric property contributions based on these Ca(2+) changes. From this, similar distributions were seen in the Ca(2+) from fluorescence measurements and the distribution of the S-parameter at a single frequency, identifying Ca(2+) as the main contributor to the electrical differences being identified. Extracted dielectric parameters also showed different distribution patterns between the untreated and ionomycin-treated groups; however, the overall electrical parameters suggest the impact of Ca(2+)-induced changes at a wider range of frequencies.