Cardiomyocytes (CM) placed on microelectrode array (MEA) were simultaneously probed with cantilever from atomic force microscope (AFM) system. This electric / nanomechanical combination in real time recorded beating force of the CMs cluster and the triggering electric events. Such "organ-on-a-chip" represents a tool for drug development and disease modeling. The human pluripotent stem cells included the WT embryonic line CCTL14 and the induced dystrophin deficient line reprogrammed from fibroblasts of a patient affected by Duchenne Muscular Dystrophy (DMD, complete loss of dystrophin expression). Both were differentiated to CMs and employed with the AFM/MEA platform for diseased CMs' drug response testing and DMD characterization. The dependence of cardiac parameters on extracellular Ca2+ was studied. The differential evaluation explained the observed effects despite variability of biological samples. The β-adrenergic stimulation (isoproterenol) and antagonist trials (verapamil) addressed ionotropic and chronotropic cell line-dependent features. For the first time, a distinctive beating-force relation for DMD CMs was measured on the 3D cardiac in vitro model.

Central European Institute of Technology Masaryk University Kamenice 5 62500 Brno Czech Republic

Central European Institute of Technology Masaryk University Kamenice 5 62500 Brno Czech Republic; International Clinical Research Centre of Saint Anne Hospital Brno Pekarska 53 60200 Brno Czech Republic; Department of Informatics Bioengineering Robotics and Systems Engineering University of Genova Via All'Opera Pia 13 16145 Genova Italy

Department of Biology Faculty of Medicine Masaryk University Kamenice 5 62500 Brno Czech Republic

Department of Informatics Bioengineering Robotics and Systems Engineering University of Genova Via All'Opera Pia 13 16145 Genova Italy

International Clinical Research Centre of Saint Anne Hospital Brno Pekarska 53 60200 Brno Czech Republic; Department of Biology Faculty of Medicine Masaryk University Kamenice 5 62500 Brno Czech Republic; 1st Department of Cardiovascular Diseases St Anne's University Hospital and Masaryk University Pekarska 53 Brno Czech Republic

References provided by Crossref.org

Salbutamol attenuates arrhythmogenic effect of aminophylline in a hPSC-derived cardiac model

Piezoelectric biosensors: shedding light on principles and applications

Cellular pathology of the human heart in Duchenne muscular dystrophy (DMD): lessons learned from in vitro modeling

Aminophylline Induces Two Types of Arrhythmic Events in Human Pluripotent Stem Cell-Derived Cardiomyocytes

DMD Pluripotent Stem Cell Derived Cardiac Cells Recapitulate in vitro Human Cardiac Pathophysiology