Non-invasive assessment of electromechanical coupling in the study of cardiomyocytes

Quantitatively assessing cardiomyocyte contractility, combined with electrophysiological measures, is essential for understanding cardiac functionality, cardiovascular diseases, and pharmacological responses. Specifically, drugs interacting with ion channels can impair heart function, affecting both mechanical contraction and electrical activity. This thesis proposes an innovative approach to simultaneously monitor these aspects by integrating non-invasive optical and electrophysiological techniques. For the analyses conducted, the signals were extracted from cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs), which are somatic cells that can be reprogrammed returning to a pluripotent state resembling embryonic stem cells. By employing the Farneback dense optical flow method to analyze videos acquired with a microscope and a camera, the cellular motion can be tracked. This provides a precise quantification of contractility, including the measurements of contraction speed and displacement. Simultaneously, a microelectrode array (MEA) system integrated with laser-poration technology allows for intracellular recording of cardiac action potentials (APs) without compromising the cell integrity. The mechanical and the bio-electrical signals were precisely synchronized thanks to a tailored trigger, integrated into the systems employed. This distinctive methodology enables both acute and long-term monitoring without damaging the cells, offering significant potential for drug screening and cardiotoxicity evaluation. The ability to correlate electrical and mechanical signals provides an innovative perspective on the electromechanical coupling of cardiomyocytes, enhancing the understanding of their physiological and pathological dynamics. Overall, this integrated approach allows for detailed analysis of cardiomyocytes’ activity in vitro, offering a comprehensive tool for exploring cellular functionality. A representative example is considered, comparing the electromechanical behavior of control cells and dofetilide-treated cells, the latter showing a noticeable prolongation of the repolarization phase and, consequently, an increase in AP duration. This approach opens a new path for the systematic assessment of these two measures that, with these techniques, are easily collected and elaborated, giving a new perspective for researchers and users who work in the pharmacological field.