D 2021

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

PEŠL, Martin, Jan PŘIBYL, Šimon KLIMOVIČ, Martin ŠČUREK, Deborah BECKEROVÁ et. al.

Basic information

Original name

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

Authors

PEŠL, Martin (203 Czech Republic, guarantor, belonging to the institution), Jan PŘIBYL (203 Czech Republic, belonging to the institution), Šimon KLIMOVIČ (203 Czech Republic, belonging to the institution), Martin ŠČUREK (203 Czech Republic, belonging to the institution), Deborah BECKEROVÁ (203 Czech Republic, belonging to the institution), Kristián BRAT (703 Slovakia, belonging to the institution), Petr SKLÁDAL (203 Czech Republic, belonging to the institution) and Vladimír ROTREKL (203 Czech Republic, belonging to the institution)

Edition

2021. vyd. Brno, Nanocon 2020, p. 404-409, 6 pp. 2021

Publisher

TANGER Ltd.

Other information

Language

English

Type of outcome

Stať ve sborníku

Field of Study

21001 Nano-materials

Country of publisher

Czech Republic

Confidentiality degree

není předmětem státního či obchodního tajemství

Publication form

electronic version available online

References:

RIV identification code

RIV/00216224:14110/21:00120083

Organization unit

Faculty of Medicine

ISBN

978-80-87294-98-7

ISSN

DOI

UT WoS

000664505500069

Keywords in English

Cardiomyocyte; contraction; arrhythmia; in vitro modeling; drug adverse events; pulmonary drugs

Tags

Tags

International impact, Reviewed
Změněno: 2/8/2023 08:02, Mgr. Tereza Miškechová

Abstract

V originále

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.

Links

LM2018127, research and development project
Name: Česká infrastruktura pro integrativní strukturní biologii (Acronym: CIISB)
Investor: Ministry of Education, Youth and Sports of the CR
MUNI/A/1455/2019, interní kód MU
Name: Arytmogenní efekt aminophyllinu na buněčné kultury kardiomyocytů
Investor: Masaryk University, Category A
NU20-06-00156, research and development project
Name: Vliv pneumologické medikace na funkce lidských kardiomyocytů.
Investor: Ministry of Health of the CR, Subprogram 1 - standard