TY  - JOUR
A1  - Goßmann, Matthias
A1  - Frotscher, Ralf
A1  - Linder, Peter
A1  - Bayer, Robin
A1  - Epple, U.
A1  - Staat, Manfred
A1  - Temiz Artmann, Aysegül
A1  - Artmann, Gerhard
T1  - Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells
JF  - Cellular physiology and biochemistry
N2  - Background/Aims: Common systems for the quantification of cellular contraction rely on animal-based models, complex experimental setups or indirect approaches. The herein presented CellDrum technology for testing mechanical tension of cellular monolayers and thin tissue constructs has the potential to scale-up mechanical testing towards medium-throughput analyses. Using hiPS-Cardiac Myocytes (hiPS-CMs) it represents a new perspective of drug testing and brings us closer to personalized drug medication. Methods: In the present study, monolayers of self-beating hiPS-CMs were grown on ultra-thin circular silicone membranes and deflect under the weight of the culture medium. Rhythmic contractions of the hiPS-CMs induced variations of the membrane deflection. The recorded contraction-relaxation-cycles were analyzed with respect to their amplitudes, durations, time integrals and frequencies. Besides unstimulated force and tensile stress, we investigated the effects of agonists and antagonists acting on Ca²⁺ channels (S-Bay K8644/verapamil) and Na⁺ channels (veratridine/lidocaine). Results: The measured data and simulations for pharmacologically unstimulated contraction resembled findings in native human heart tissue, while the pharmacological dose-response curves were highly accurate and consistent with reference data. Conclusion: We conclude that the combination of the CellDrum with hiPS-CMs offers a fast, facile and precise system for pharmacological, toxicological studies and offers new preclinical basic research potential.
KW  - Inotropic compounds
KW  - Pharmacology
KW  - Ion channels
KW  - CellDrum
KW  - Heart tissue culture
KW  - Induced pluripotent stem cells
KW  - Cardiac myocytes
Y1  - 2016
U6  - http://dx.doi.org/10.1159/000443124
SN  - 1421-9778 (Online)
SN  - 1015-8987 (Print)
VL  - 38
IS  - 3
SP  - 1182
EP  - 1198
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Temiz Artmann, Aysegül
A1  - Kurulgan demirci, Eylem
A1  - Fırat, Ipek Seda
A1  - Oflaz, Hakan
A1  - Artmann, Gerhard
T1  - Recombinant activated protein C (rhAPC) affects lipopolysaccharide-induced mechanical compliance changes and beat frequency of mESC-derived cardiomyocyte monolayers
JF  - SHOCK
KW  - Septic cardiomyopathy
KW  - LPS
KW  - cardiomyocyte biomechanics
KW  - CellDrum
KW  - actin cytoskeleton
Y1  - 2021
U6  - http://dx.doi.org/10.1097/SHK.0000000000001845
SN  - 1540-0514
PB  - Wolters Kluwer
CY  - Köln
ER  - 
TY  - JOUR
A1  - Kurulgan Demirci, Eylem
A1  - Demirci, Taylan
A1  - Linder, Peter
A1  - Trzewik, Jürgen
A1  - Gierkowski, Jessica Ricarda
A1  - Gossmann, Matthias
A1  - Kayser, Peter
A1  - Porst, Dariusz
A1  - Digel, Ilya
A1  - Artmann, Gerhard
A1  - Temiz Artmann, Aysegül
T1  - rhAPC reduces the endothelial cell permeability via a decrease of contractile tensions induced by endothelial cells
JF  - Journal of Bioscience and Bioengineering
N2  - All cells generate contractile tension. This strain is crucial for mechanically controlling the cell shape, function and survival. In this study, the CellDrum technology quantifying cell's (the cellular) mechanical tension on a pico-scale was used to investigate the effect of lipopolysaccharide (LPS) on human aortic endothelial cell (HAoEC) tension. The LPS effect during gram-negative sepsis on endothelial cells is cell contraction causing endothelium permeability increase. The aim was to finding out whether recombinant activated protein C (rhAPC) would reverse the endothelial cell response in an in-vitro sepsis model. In this study, the established in-vitro sepsis model was confirmed by interleukin 6 (IL-6) levels at the proteomic and genomic levels by ELISA, real time-PCR and reactive oxygen species (ROS) activation by florescence staining. The thrombin cellular contraction effect on endothelial cells was used as a positive control when the CellDrum technology was applied. Additionally, the Ras homolog gene family, member A (RhoA) mRNA expression level was checked by real time-PCR to support contractile tension results. According to contractile tension results, the mechanical predominance of actin stress fibers was a reason of the increased endothelial contractile tension leading to enhanced endothelium contractility and thus permeability enhancement. The originality of this data supports firstly the basic measurement principles of the CellDrum technology and secondly that rhAPC has a beneficial effect on sepsis influenced cellular tension. The technology presented here is promising for future high-throughput cellular tension analysis that will help identify pathological contractile tension responses of cells and prove further cell in-vitro models.
KW  - Cell permeability
KW  - Cellular force
KW  - Endothelial cells
KW  - Recombinant activated protein C
KW  - Lipopolysaccharide
KW  - Contractile tension
KW  - CellDrum
Y1  - 2012
U6  - http://dx.doi.org/10.1016/j.jbiosc.2012.03.019
SN  - 1347-4421
VL  - 113
IS  - 2
SP  - 212
EP  - 219
PB  - Elsevier
CY  - Amsterdam
ER  -