Atomic force microscopy combined with human pluripotent stem cell derived cardiomyocytes for biomechanical sensing.
Cardiomyocyte contraction and relaxation are important parameters of cardiac function altered in many heart pathologies. Biosensing of these parameters represents an important tool in drug development and disease modeling. Human embryonic stem cells and especially patient specific induced pluripotent stem cell-derived cardiomyocytes are well established as cardiac disease model.. Here, a live stem cell derived embryoid body (EB) based cardiac cell syncytium served as a biorecognition element coupled to the microcantilever probe from atomic force microscope thus providing reliable micromechanical cellular biosensor suitable for whole-day testing. The biosensor was optimized regarding the type of cantilever, temperature and exchange of media; in combination with standardized protocol, it allowed testing of compounds and conditions affecting the biomechanical properties of EB. The studied effectors included calcium , drugs modulating the catecholaminergic fight-or-flight stress response such as the beta-adrenergic blocker metoprolol and the beta-adrenergic agonist isoproterenol. Arrhythmogenic effects were studied using caffeine. Furthermore, with EBs originating from patient's stem cells, this biosensor can help to characterize heart diseases such as dystrophies.
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; ICRC, St. Anne's University Hospital, Brno, Czech Republic.
Martin
M
Pesl
CEITEC, Masaryk University, Brno, Czech Republic.
Jan
J
Pribyl
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Ivana
I
Acimovic
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Aleksandra
A
Vilotic
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Sarka
S
Jelinkova
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; ICRC, St. Anne's University Hospital, Brno, Czech Republic.
Anton
A
Salykin
PhyMedExp, INSERM U1046, University of Montpellier, Montpellier, France.
Alain
A
Lacampagne
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; ICRC, St. Anne's University Hospital, Brno, Czech Republic.
Petr
P
Dvorak
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; PhyMedExp, INSERM U1046, University of Montpellier, Montpellier, France.
Albano C
AC
Meli
CEITEC, Masaryk University, Brno, Czech Republic. Electronic address: skladal@chemi.muni.cz.
Petr
P
Skladal
Department of Biology, Faculty of Medicine, Masaryk University, Brno, Czech Republic; ICRC, St. Anne's University Hospital, Brno, Czech Republic.
Vladimir
V
Rotrekl
D058671:Adrenergic beta-1 Receptor Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D001696:Biomechanical Phenomena / Q000187:drug effects; D015374:Biosensing Techniques / Q000295:instrumentation / Q000379:methods*; D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D004867:Equipment Design; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008790:Metoprolol / Q000494:pharmacology; D018625:Microscopy, Atomic Force / Q000295:instrumentation / Q000379:methods*; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D039904:Pluripotent Stem Cells / Q000166:cytology
D058671:Adrenergic beta-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D008790:Metoprolol; D007545:Isoproterenol
Cardiomyocyte contraction; Drug testing; Human stem cell; Micromechanical biosensor