TY - JOUR A1 - Hunker, Jan L. A1 - Gossmann, Matthias A1 - Raman, Aravind Hariharan A1 - Linder, Peter T1 - Artificial neural networks in cardiac safety assessment: Classification of chemotherapeutic compound effects on hiPSC-derived cardiomyocyte contractility JF - Journal of Pharmacological and Toxicological Methods Y1 - 2021 U6 - http://dx.doi.org/10.1016/j.vascn.2021.107044 SN - 1056-8719 VL - 111 IS - Article number 107044 PB - Elsevier CY - New York ER - TY - JOUR A1 - Gossmann, Matthias A1 - Thomas, Ulrich A1 - Horváth, András A1 - Dragicevic, Elena A1 - Stoelzle-Feix, Sonja A1 - Jung, Alexander A1 - Raman, Aravind Hariharan A1 - Staat, Manfred A1 - Linder, Peter T1 - A higher-throughput approach to investigate cardiac contractility in vitro under physiological mechanical conditions JF - Journal of Pharmacological and Toxicological Methods Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.vascn.2020.106843 VL - 105 IS - Article 106843 PB - Elsevier CY - New York, NY ER - TY - JOUR A1 - Knox, Ronald A1 - Bruggemann, Andrea A1 - Gossmann, Matthias A1 - Thomas, Ulrich A1 - Horváth, András A1 - Dragicevic, Elena A1 - Stoelzle-Feix, Sonja A1 - Fertig, Niels A1 - Jung, Alexander A1 - Raman, Aravind Hariharan A1 - Staat, Manfred A1 - Linder, Peter T1 - Combining physiological relevance and throughput for in vitro cardiac contractility measurement JF - Biophysical Journal N2 - Despite increasing acceptance of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in safety pharmacology, controversy remains about the physiological relevance of existing in vitro models for their mechanical testing. We hypothesize that existing signs of immaturity of the cell models result from an improper mechanical environment. We cultured hiPSC-CMs in a 96-well format on hyperelastic silicone membranes imitating their native mechanical environment, resulting in physiological responses to compound stimuli.We validated cell responses on the FLEXcyte 96, with a set of reference compounds covering a broad range of cellular targets, including ion channel modulators, adrenergic receptor modulators and kinase inhibitors. Acute (10 - 30 min) and chronic (up to 7 days) effects were investigated. Furthermore, the measurements were complemented with electromechanical models based on electrophysiological recordings of the used cell types.hiPSC-CMs were cultured on freely-swinging, ultra-thin and hyperelastic silicone membranes. The weight of the cell culture medium deflects the membranes downwards. Rhythmic contraction of the hiPSC-CMs resulted in dynamic deflection changes which were quantified by capacitive distance sensing. The cells were cultured for 7 days prior to compound addition. Acute measurements were conducted 10-30 minutes after compound addition in standard culture medium. For chronic treatment, compound-containing medium was replaced daily for up to 7 days. Electrophysiological properties of the employed cell types were recorded by automated patch-clamp (Patchliner) and the results were integrated into the electromechanical model of the system.Calcium channel agonist S Bay K8644 and beta-adrenergic stimulator isoproterenol induced significant positive inotropic responses without additional external stimulation. Kinase inhibitors displayed cardiotoxic effects on a functional level at low concentrations. The system-integrated analysis detected alterations in beating shape as well as frequency and arrhythmic events and we provide a quantitative measure of these. Y1 - 2020 U6 - http://dx.doi.org/10.1016/j.bpj.2019.11.3104 SN - 0006-3495 N1 - Raman, Arayind Hariharan im Artikel unter dem Namen: Raman, Alexander H. VL - 118 IS - Issue 3, Supplement 1 SP - 570a PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Linder, Peter A1 - Beckler, Matthias A1 - Doerr, Leo A1 - Stoelzle-Feix, Sonja A1 - Fertig, Niels A1 - Jung, Alexander A1 - Staat, Manfred A1 - Gossmann, Matthias T1 - A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions JF - Journal of Pharmacological and Toxicological Methods Y1 - 2019 U6 - http://dx.doi.org/10.1016/j.vascn.2019.05.162 SN - 1056-8719 VL - 99 IS - Article number 106595 PB - Elsevier CY - Amsterdam ER - 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 - Kowalski, Julia A1 - Linder, Peter A1 - Zierke, S. A1 - Wulfen, B. van A1 - Clemens, J. A1 - Konstantinidis, K. A1 - Ameres, G. A1 - Hoffmann, R. A1 - Mikucki, J. A1 - Tulaczyk, S. A1 - Funke, O. A1 - Blandfort, D. A1 - Espe, Clemens A1 - Feldmann, Marco A1 - Francke, Gero A1 - Hiecker, S. A1 - Plescher, Engelbert A1 - Schöngarth, Sarah A1 - Dachwald, Bernd A1 - Digel, Ilya A1 - Artmann, Gerhard A1 - Eliseev, D. A1 - Heinen, D. A1 - Scholz, F. A1 - Wiebusch, C. A1 - Macht, S. A1 - Bestmann, U. A1 - Reineking, T. A1 - Zetzsche, C. A1 - Schill, K. A1 - Förstner, R. A1 - Niedermeier, H. A1 - Szumski, A. A1 - Eissfeller, B. A1 - Naumann, U. A1 - Helbing, K. T1 - Navigation technology for exploration of glacier ice with maneuverable melting probes JF - Cold Regions Science and Technology N2 - The Saturnian moon Enceladus with its extensive water bodies underneath a thick ice sheet cover is a potential candidate for extraterrestrial life. Direct exploration of such extraterrestrial aquatic ecosystems requires advanced access and sampling technologies with a high level of autonomy. A new technological approach has been developed as part of the collaborative research project Enceladus Explorer (EnEx). The concept is based upon a minimally invasive melting probe called the IceMole. The force-regulated, heater-controlled IceMole is able to travel along a curved trajectory as well as upwards. Hence, it allows maneuvers which may be necessary for obstacle avoidance or target selection. Maneuverability, however, necessitates a sophisticated on-board navigation system capable of autonomous operations. The development of such a navigational system has been the focal part of the EnEx project. The original IceMole has been further developed to include relative positioning based on in-ice attitude determination, acoustic positioning, ultrasonic obstacle and target detection integrated through a high-level sensor fusion. This paper describes the EnEx technology and discusses implications for an actual extraterrestrial mission concept. Y1 - 2016 U6 - http://dx.doi.org/10.1016/j.coldregions.2015.11.006 SN - 0165-232X IS - 123 SP - 53 EP - 70 PB - Elsevier CY - Amsterdam ER - TY - JOUR A1 - Micili, Serap C. A1 - Valter, Markus A1 - Oflaz, Hakan A1 - Ozogul, Candan A1 - Linder, Peter A1 - Föckler, Nicole A1 - Artmann, Gerhard A1 - Digel, Ilya A1 - Temiz Artmann, Aysegül T1 - Optical coherence tomography : a potential tool to predict premature rupture of fetal membranes JF - Proceedings of the Institution of Mechanical Engineers. Part H : Journal of engineering in medicine Y1 - 2013 SN - 0046-2039 (Print) ; 2041-3033 (E-Journal) VL - Vol. 227 IS - No. 4 SP - 393 EP - 401 PB - Sage CY - London ER - TY - JOUR A1 - Digel, Ilya A1 - Dachwald, Bernd A1 - Artmann, Gerhard A1 - Linder, Peter A1 - Funke, O. T1 - A concept of a probe for particle analysis and life detection in icy environments Y1 - 2009 N1 - International workshop “Europa lander: science goals and experiments”, Space Research Institute (IKI), Moscow, Russia 9-13 February 2009 SP - 1 EP - 24 ER - TY - JOUR A1 - Kurulgan Demirci, Eylem A1 - Linder, Peter A1 - Demirci, Taylan A1 - Trzewik, Jürgen A1 - Digel, Ilya A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül T1 - Contractile tension of endothelial cells: An LPS based in-vitro sepsis model JF - IUBMB Life. 61 (2009), H. 3 Y1 - 2009 SN - 1521-6543 N1 - Abstracts: Turkish Society of Molecular Medicine, Third International Congress of Molecular Medicine, May 5-8, 2009, Istanbul, Turkey SP - 307 EP - 308 PB - Wiley CY - Weinheim ER - TY - JOUR A1 - Artmann, Gerhard A1 - Digel, Ilya A1 - Linder, Peter A1 - Porst, Dariusz T1 - Mechanism of haemoglobin sensing body temperature JF - Tissue Engineering Part A. 14 (2008), H. 5 Y1 - 2008 SN - 1937-3341 N1 - TERMIS EU 2008 Porto Meeting June 22–26, 2008 Porto Congress Center–Alfândega Portugal SP - 754 EP - 754 ER - TY - JOUR A1 - Trzewik, Jürgen A1 - Temiz Artmann, Aysegül A1 - Linder, Peter A1 - Demirci, T. A1 - Digel, Ilya A1 - Artmann, Gerhard T1 - Evaluation of lateral mechanical tension in thin-film tissue constructs JF - Annals of Biomedical Engineering. 32 (2004), H. 9 Y1 - 2004 SN - 1573-9686 SP - 1243 EP - 1251 ER - TY - JOUR A1 - Zerlin, Kay A1 - Kasischke, Nicole A1 - Digel, Ilya A1 - Maggakis-Kelemen, Christina A1 - Temiz Artmann, Aysegül A1 - Porst, Dariusz A1 - Kayser, Peter A1 - Linder, Peter A1 - Artmann, Gerhard T1 - Structural transition temperature of hemoglobins correlates with species’ body temperature JF - European Biophysics Journal. 37 (2007), H. 1 Y1 - 2007 SN - 1432-1017 SP - 1 EP - 10 ER - TY - JOUR A1 - Digel, Ilya A1 - Kurulgan Demirci, Eylem A1 - Linder, Peter A1 - Kayser, Peter T1 - Decrease in extracellular collagen crosslinking after NMR magnetic field application in skin fibroblasts JF - Medical and Biological Engineering and Computing. 45 (2007), H. 1 Y1 - 2007 SN - 1741-0444 SP - 91 EP - 97 ER - TY - JOUR A1 - Digel, Ilya A1 - Maggakis-Kelemen, Christina A1 - Zerlin, Kay A1 - Linder, Peter T1 - Body temperature-related structural transitions of monotremal and human hemoglobin JF - Biophysical Journal. 91 (2006), H. 8 Y1 - 2006 SN - 1542-0086 SP - 3014 EP - 3021 ER - TY - JOUR A1 - Kurz, R. A1 - Linder, Peter A1 - Trzewik, Jürgen A1 - Rüffer, M. A1 - Artmann, Gerhard A1 - Digel, Ilya A1 - Rothermel, A. A1 - Robitzki, A. A1 - Temiz Artmann, Aysegül T1 - Contractile tension and beating rates of self-exciting monolayers and 3D-tissue constructs of neonatal rat cardiomyocytes JF - Medical and Biological Engineering and Computing N2 - The CellDrum technology (The term 'CellDrum technology' includes a couple of slightly different technological setups for measuring lateral mechanical tension in various types of cell monolayers or 3D-tissue constructs) was designed to quantify the contraction rate and mechanical tension of self-exciting cardiac myocytes. Cells were grown either within flexible, circular collagen gels or as monolayer on top of respective 1-mum thin silicone membranes. Membrane and cells were bulged outwards by air pressure. This biaxial strain distribution is rather similar the beating, blood-filled heart. The setup allowed presetting the mechanical residual stress level externally by adjusting the centre deflection, thus, mimicking hypertension in vitro. Tension was measured as oscillating differential pressure change between chamber and environment. A 0.5-mm thick collagen-cardiac myocyte tissue construct induced after 2 days of culturing (initial cell density 2 x 10(4) cells/ml), a mechanical tension of 1.62 +/- 0.17 microN/mm(2). Mechanical load is an important growth regulator in the developing heart, and the orientation and alignment of cardiomyocytes is stress sensitive. Therefore, it was necessary to develop the CellDrum technology with its biaxial stress-strain distribution and defined mechanical boundary conditions. Cells were exposed to strain in two directions, radially and circumferentially, which is similar to biaxial loading in real heart tissues. Thus, from a biomechanical point of view, the system is preferable to previous setups based on uniaxial stretching. Y1 - 2010 U6 - http://dx.doi.org/10.1007/s11517-009-0552-y SN - 1741-0444 VL - 48 IS - 1 SP - 59 EP - 65 PB - Springer Nature CY - Cham 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 - TY - JOUR A1 - Kurulgan Demirci, Eylem A1 - Demirci, T. A1 - Trzewik, Jürgen A1 - Linder, Peter A1 - Karakulah, G. A1 - Artmann, Gerhard A1 - Sakizli, M. A1 - Temiz Artmann, Aysegül T1 - Genome-Wide Gene Expression Analysis of NIH 3T3 Cell Line Under Mechanical Stimulation JF - Cellular and molecular bioengineering. 4 (2011), H. 1 Y1 - 2011 SN - 1865-5025 SP - 46 EP - 55 PB - Springer CY - Berlin ER - TY - JOUR A1 - Linder, Peter A1 - Digel, Ilya A1 - Temiz Artmann, Aysegül A1 - Kayser, Peter A1 - Porst, Dariusz A1 - Artmann, Gerhard T1 - High-throughput testing of mechanical forces generated in thin cell and tissue layers JF - Tissue Engineering. 13 (2007), H. 7 Y1 - 2007 SN - 1076-3279 N1 - Meeting abstract 433 SP - 1778 EP - 1778 ER - TY - JOUR A1 - Demirci, Taylan A1 - Kurulgan Demirci, Eylem A1 - Trzewik, Jürgen A1 - Linder, Peter A1 - Digel, Ilya A1 - Artmann, Gerhard A1 - Sakizli, Meral A1 - Temiz Artmann, Aysegül T1 - Gene expression profile analysis of 3T3/NIH fibroblasts after one hour mechanical stress JF - IUBMB Life. 61 (2009), H. 3 Y1 - 2009 SN - 1521-6543 N1 - Abstracts: Turkish Society of Molecular Medicine, Third International Congress of Molecular Medicine, May 5-8, 2009, Istanbul, Turkey SP - 311 EP - 312 PB - Wiley-VCH CY - Weinheim ER - TY - JOUR A1 - Demirci, T. A1 - Trzewik, J. A1 - Linder, Peter A1 - Digel, Ilya A1 - Artmann, Gerhard A1 - Temiz Artmann, Aysegül T1 - Mechanical Stimulation of 3T3 Fibroblasts Activates Genes: ITGB5 and p53 Responses as Quantified on the mRNA Level JF - Biomedizinische Technik . 49 (2004), H. Erg.-Bd. 2 Y1 - 2004 SN - 0932-4666 SP - 1030 EP - 1031 ER -