title: Non-Invasive Acoustical sensing of Drug-Induced Effects on the Contractile Machinery of Human Cardiomyocyte Clusters.
abstract: There is an urgent need for improved models for cardiotoxicity testing. Here we propose acoustic sensing applied to beating human cardiomyocyte clusters for non-invasive, surrogate measuring of the QT interval and other characteristics of the contractile machinery. In experiments with the acoustic method quartz crystal microbalance with dissipation monitoring (QCM-D), the shape of the recorded signals was very similar to the extracellular field potential detected in electrochemical experiments, and the expected changes of the QT interval in response to addition of conventional drugs (E-4031 or nifedipine) were observed. Additionally, changes in the dissipation signal upon addition of cytochalasin D were in good agreement with the known, corresponding shortening of the contraction-relaxation time. These findings suggest that QCM-D has great potential as a tool for cardiotoxicological screening, where effects of compounds on the cardiomyocyte contractile machinery can be detected independently of whether the extracellular field potential is altered or not.
authors.affiliation: Department of Applied Physics, Chalmers University of Technology, Göteborg, Sweden.
authors.forename: Angelika
authors.initials: A
authors.lastname: Kunze
authors.affiliation: Cellectis AB, Göteborg, Sweden.
authors.forename: Daniella
authors.initials: D
authors.lastname: Steel
authors.affiliation: Cellectis AB, Göteborg, Sweden.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Dahlenborg
authors.affiliation: Cellectis AB, Göteborg, Sweden; Systems Biology Research Center, School of Bioscience, University of Skövde, Skövde, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Sartipy
authors.affiliation: Department of Applied Physics, Chalmers University of Technology, Göteborg, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Svedhem
mesh_terms: D015374:Biosensing Techniques / Q000379:methods; D002460:Cell Line; D015638:Cytochalasin D / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism*; D009543:Nifedipine; D010880:Piperidines / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D058525:Quartz Crystal Microbalance Techniques
chemical_list: D010880:Piperidines; D011725:Pyridines; C063968:E 4031; D015638:Cytochalasin D; D009543:Nifedipine; D007545:Isoproterenol