CELL BASED AFM BIOSENSENSING FOR SCREENING OF PULMONARY-DRUG RELATED ARRHYTMIC EFFECTS

1,2,3 PESL Martin
Co-authors:
4 PRIBYL Jan 4 KLIMOVIC Simon 5 SCUREK Martin 1,2 BECKEROVÁ Deborah 5 BRAT Kristian 4,6 SKLADAL Petr 1,2 ROTREKL Vladimir
Institutions:
1 ICRC, St. Anna University Hospital, Czech Republic, EU
2 Department of Biology, Medical faculty, Masaryk University, Czech Republic, EU
3 1st Internal medicine clinic-Cardio-angiology, St. Anna University Hospital/Masaryk University, Czech Republic, EU
4 Nanobiotechnology, CEITEC MU, Czech Republic, EU
5 Dept. of Respiratory Diseases, University Hospital Brno and Faculty of Medicine, Masaryk University, Czech Republic, EU
6 Dept. of Biochemistry, Faculty of Science, Masaryk University, Czech Republic, EU
Conference:
12th International Conference on Nanomaterials - Research & Application, Brno, Czech Republic, EU, October 21 - 23, 2020
Proceedings:
Proceedings 12th International Conference on Nanomaterials - Research & Application
Pages:
404-409
ISBN:
978-80-87294-98-7
ISSN:
2694-930X
Published:
28th December 2020
Proceedings of the conference were published in Web of Science and Scopus.
Metrics:
264 views / 136 downloads
Abstract

Atomic force microscopy (AFM) combined with stem cell derived human cardiomyocytes (CM) enables dynamic follow-up of cardiac contractions (e.g. beating rate, contraction and relaxation times), simultaneously with other CM biomechanical properties. Today, majority of drugs entering clinical usage needs to be tested for adverse arrhythmic effects; nevertheless, the effects on cardiomyocyte contraction are not routinely employed, only when related to cardiac pathologies. AFM-based biosensor allows in-vitro disease modeling, but also enables to monitor the effect of CM-contraction affecting drugs. Until today only few selected drugs modulating contractility and spontaneous pacing were described in animal models. This work for the first time demonstrates that basic biomechanical parameters, such as average value of contraction force and the beat rate, represent valuable pharmacological indicators of different phenotypic effects on cells without genetic burden. The presented method is robust and has low computational requirements, while keeping optimal spatial sensitivity (force detection limit 200 pN, corresponding to 20 nm displacement). The cardiac stimulating activities of drugs utilized in pneumology as aminophylline, ipratropium, and salbutamol were tested. Stimulating drugs, e.g. methylxanthines and caffeine, presented aberrant cardiomyocyte response, confirming arrhythmogenic potential, and force related fluctuations. Quantification of spontaneous contraction irregularities and related contractility changes allow precise scaling of potential negative effects adding new safety level to clinically relevant drug testing. AFM combined with human CMs serve as robust real-time screening platform for effects of pulmonary drugs. Here we describe changes in CM contractility, which is hard to describe by other screening methods and was never tested with described medication.

Keywords: Cardiomyocyte, contraction, arrhythmia, in vitro modeling, drug adverse events, pulmonary drugs

© This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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