hESC derived cardiomyocyte biosensor to detect the different types of arrhythmogenic properties of drugs

Authors

PIVATO Roberto KLIMOVIČ Šimon KABANOV Daniil SVĚRÁK Filip PEŠL Martin PŘIBYL Jan ROTREKL Vladimír

Year of publication 2022
Type Article in Periodical
Magazine / Source Analytica Chimica Acta
MU Faculty or unit

Faculty of Medicine

Citation
Web https://www.sciencedirect.com/science/article/pii/S000326702200530X
Doi http://dx.doi.org/10.1016/j.aca.2022.339959
Keywords Cell-based biosensor; Atomic force microscopy; Human embryonic stem cells; Cardiac arrhythmia; Cardiomyocytes; Caffeine
Attached files
Description In the present work, we introduce a new cell-based biosensor for detecting arrhythmias based on a novel utilization of the combination of the Atomic Force Microscope (AFM) lateral force measurement as a nanosensor with a dual 3D cardiomyocyte syncytium. Two spontaneously coupled clusters of cardiomyocytes form this. The syncytium's functional contraction behavior was assessed using video sequences analyzed with Musclemotion ImageJ/Fiji software, and immunocytochemistry evaluated phenotype composition. The application of caffeine solution induced arrhythmia as a model drug, and its spontaneous resolution was monitored by AFM lateral force recording and interpretation and calcium fluorescence imaging as a reference method describing non-synchronized contractions of cardiomyocytes. The phenotypic analysis revealed the syncytium as a functional contractile and conduction cardiac behavior model. Calcium fluorescence imaging was used to validate that AFM fully enabled to discriminate cardiac arrhythmias in this in vitro cellular model. The described novel 3D hESCs-based cellular biosensor is suitable to detect arrhythmic events on the level of cardiac contractile and conduction tissue cellular model. The resulting biosensor allows for screening of arrhythmogenic properties of tailored drugs enabling its use in precision medicine.
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