Cell based AFM biosensensing for screening of pulmonary-drug related arrhytmic effects

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00159816%3A_____%2F21%3A00074466" target="_blank" >RIV/00159816:_____/21:00074466 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/65269705:_____/21:00074466 RIV/00216224:14110/21:00120083

Výsledek na webu

<a href="http://dx.doi.org/10.37904/nanocon.2020.3745" target="_blank" >http://dx.doi.org/10.37904/nanocon.2020.3745</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.37904/nanocon.2020.3745" target="_blank" >10.37904/nanocon.2020.3745</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Cell based AFM biosensensing for screening of pulmonary-drug related arrhytmic effects

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Cell based AFM biosensensing for screening of pulmonary-drug related arrhytmic effects

Popis výsledku anglicky

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.

Druh

D - Stať ve sborníku

CEP obor

—

OECD FORD obor

21002 - Nano-processes (applications on nano-scale); (biomaterials to be 2.9)

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2021

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název statě ve sborníku

Proceedings 12th International Conference on Nanomaterials - Research &amp; Application

ISBN

978-80-87294-98-7

ISSN

—

e-ISSN

—

Počet stran výsledku

6

Strana od-do

404-409

Název nakladatele

TANGER LTD

Místo vydání

Ostrava

Místo konání akce

Brno

Datum konání akce

21. 10. 2020

Typ akce podle státní příslušnosti

WRD - Celosvětová akce

Kód UT WoS článku

000664505500069