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@inproceedings{1730000,
author = {Pešl, Martin and Přibyl, Jan and Klimovič, Šimon and Ščurek, Martin and Beckerová, Deborah and Brat, Kristián and Skládal, Petr and Rotrekl, Vladimír},
address = {Brno},
booktitle = {Nanocon 2020},
doi = {http://dx.doi.org/10.37904/nanocon.2020.3745},
edition = {2021},
keywords = {Cardiomyocyte; contraction; arrhythmia; in vitro modeling; drug adverse events; pulmonary drugs},
howpublished = {elektronická verze "online"},
language = {eng},
location = {Brno},
isbn = {978-80-87294-98-7},
pages = {404-409},
publisher = {TANGER Ltd.},
title = {Cell based AFM biosensensing for screening of pulmonary-drug related arrhytmic effects},
url = {https://www.confer.cz/nanocon/2020/3745-cell-based-afm-biosensensing-for-screening-of-pulmonary-drug-related-arrhytmic-effects},
year = {2021}
}
TY - JOUR
ID - 1730000
AU - Pešl, Martin - Přibyl, Jan - Klimovič, Šimon - Ščurek, Martin - Beckerová, Deborah - Brat, Kristián - Skládal, Petr - Rotrekl, Vladimír
PY - 2021
TI - Cell based AFM biosensensing for screening of pulmonary-drug related arrhytmic effects
PB - TANGER Ltd.
CY - Brno
SN - 9788087294987
KW - Cardiomyocyte
KW - contraction
KW - arrhythmia
KW - in vitro modeling
KW - drug adverse events
KW - pulmonary drugs
UR - https://www.confer.cz/nanocon/2020/3745-cell-based-afm-biosensensing-for-screening-of-pulmonary-drug-related-arrhytmic-effects
N2 - 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.
ER -
PEŠL, Martin, Jan PŘIBYL, Šimon KLIMOVIČ, Martin ŠČUREK, Deborah BECKEROVÁ, Kristián BRAT, Petr SKLÁDAL and Vladimír ROTREKL. Cell based AFM biosensensing for screening of pulmonary-drug related arrhytmic effects. Online. In \textit{Nanocon 2020}. 2021st ed. Brno: TANGER Ltd., 2021, p.~404-409. ISBN~978-80-87294-98-7. Available from: https://dx.doi.org/10.37904/nanocon.2020.3745.
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