@article{GossmannThomasHorvathetal.2020, author = {Gossmann, Matthias and Thomas, Ulrich and Horv{\´a}th, Andr{\´a}s and Dragicevic, Elena and Stoelzle-Feix, Sonja and Jung, Alexander and Raman, Aravind Hariharan and Staat, Manfred and Linder, Peter}, title = {A higher-throughput approach to investigate cardiac contractility in vitro under physiological mechanical conditions}, series = {Journal of Pharmacological and Toxicological Methods}, volume = {105}, journal = {Journal of Pharmacological and Toxicological Methods}, number = {Article 106843}, publisher = {Elsevier}, address = {New York, NY}, doi = {10.1016/j.vascn.2020.106843}, year = {2020}, language = {en} } @article{LinderBecklerDoerretal.2019, author = {Linder, Peter and Beckler, Matthias and Doerr, Leo and Stoelzle-Feix, Sonja and Fertig, Niels and Jung, Alexander and Staat, Manfred and Gossmann, Matthias}, title = {A new in vitro tool to investigate cardiac contractility under physiological mechanical conditions}, series = {Journal of Pharmacological and Toxicological Methods}, volume = {99}, journal = {Journal of Pharmacological and Toxicological Methods}, number = {Article number 106595}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1056-8719}, doi = {10.1016/j.vascn.2019.05.162}, year = {2019}, language = {en} } @article{HunkerGossmannRamanetal.2021, author = {Hunker, Jan L. and Gossmann, Matthias and Raman, Aravind Hariharan and Linder, Peter}, title = {Artificial neural networks in cardiac safety assessment: Classification of chemotherapeutic compound effects on hiPSC-derived cardiomyocyte contractility}, series = {Journal of Pharmacological and Toxicological Methods}, volume = {111}, journal = {Journal of Pharmacological and Toxicological Methods}, number = {Article number 107044}, publisher = {Elsevier}, address = {New York}, issn = {1056-8719}, doi = {10.1016/j.vascn.2021.107044}, year = {2021}, language = {en} } @misc{ArtmannLinderBayeretal.2017, author = {Artmann, Gerhard and Linder, Peter and Bayer, Robin and Gossmann, Matthias}, title = {Celldrum electrode arrangement for measuring mechanical stress [Patent of invention]}, publisher = {WIPO}, address = {Geneva}, pages = {18 Seiten}, year = {2017}, abstract = {The invention pertains to a CellDrum electrode arrangement for measuring mechanical stress, comprising a mechanical holder (1 ) and a non-conductive membrane (4), whereby the membrane (4) is at least partially fixed at its circumference to the mechanical holder (1), keeping it in place when the membrane (4) may bend due to forces acting on the membrane (4), the mechanical holder (1) and the membrane (4) forming a container, whereby the membrane (1) within the container comprises an cell- membrane compound layer or biological material (3) adhered to the deformable membrane 4 which in response to stimulation by an agent may exert mechanical stress to the membrane (4) such that the membrane bending stage changes whereby the container may be filled with an electrolyte, whereby an electric contact (2) is arranged allowing to contact said electrolyte when filled into to the container, whereby within a predefined geometry to the fixing of the membrane (4) an electrode (7) is arranged, whereby the electrode (7) is electrically insulated with respect to the electric contact (2) as well as said electrolyte, whereby mechanical stress due to an agent may be measured as a change in capacitance.}, language = {en} } @article{KnoxBruggemannGossmannetal.2020, author = {Knox, Ronald and Bruggemann, Andrea and Gossmann, Matthias and Thomas, Ulrich and Horv{\´a}th, Andr{\´a}s and Dragicevic, Elena and Stoelzle-Feix, Sonja and Fertig, Niels and Jung, Alexander and Raman, Aravind Hariharan and Staat, Manfred and Linder, Peter}, title = {Combining physiological relevance and throughput for in vitro cardiac contractility measurement}, series = {Biophysical Journal}, volume = {118}, journal = {Biophysical Journal}, number = {Issue 3, Supplement 1}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0006-3495}, doi = {10.1016/j.bpj.2019.11.3104}, pages = {570a}, year = {2020}, abstract = {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.}, language = {en} } @article{SeifarthGossmannGrosseetal.2015, author = {Seifarth, Volker and Goßmann, Matthias and Grosse, J. O. and Becker, C. and Heschel, I. and Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l}, title = {Development of a Bioreactor to Culture Tissue Engineered Ureters Based on the Application of Tubular OPTIMAIX 3D Scaffolds}, series = {Urologia Internationalis}, volume = {2015}, journal = {Urologia Internationalis}, number = {95}, publisher = {Karger}, address = {Basel}, issn = {0042-1138}, doi = {10.1159/000368419}, pages = {106 -- 113}, year = {2015}, language = {en} } @inproceedings{HunkerJungGossmannetal.2019, author = {Hunker, Jan and Jung, Alexander and Goßmann, Matthias and Linder, Peter and Staat, Manfred}, title = {Development of a tool to analyze the conduction speed in microelectrode array measurements of cardiac tissue}, series = {3rd YRA MedTech Symposium 2019 : May 24 / 2019 / FH Aachen}, booktitle = {3rd YRA MedTech Symposium 2019 : May 24 / 2019 / FH Aachen}, editor = {Staat, Manfred and Erni, Daniel}, publisher = {Universit{\"a}t Duisburg-Essen}, address = {Duisburg}, organization = {MedTech Symposium}, isbn = {978-3-940402-22-6}, doi = {10.17185/duepublico/48750}, pages = {7 -- 8}, year = {2019}, abstract = {The discovery of human induced pluripotent stem cells reprogrammed from somatic cells [1] and their ability to differentiate into cardiomyocytes (hiPSC-CMs) has provided a robust platform for drug screening [2]. Drug screenings are essential in the development of new components, particularly for evaluating the potential of drugs to induce life-threatening pro-arrhythmias. Between 1988 and 2009, 14 drugs have been removed from the market for this reason [3]. The microelectrode array (MEA) technique is a robust tool for drug screening as it detects the field potentials (FPs) for the entire cell culture. Furthermore, the propagation of the field potential can be examined on an electrode basis. To analyze MEA measurements in detail, we have developed an open-source tool.}, language = {en} } @phdthesis{Gossmann2015, author = {Goßmann, Matthias}, title = {Entwicklung eines autokontraktilen Herzmuskelmodells zur funktionalen Medikamenten- und Toxinforschung}, publisher = {Universit{\"a}tsbibliothek Duisburg-Essen}, address = {Duisburg ; Essen}, year = {2015}, language = {de} } @article{LeimenaArtmannDachwaldetal.2010, author = {Leimena, W. and Artmann, Gerhard and Dachwald, Bernd and Temiz Artmann, Ayseg{\"u}l and Gossmann, Matthias and Digel, Ilya}, title = {Feasibility of an in-situ microbial decontamination of an ice-melting probe}, series = {Eurasian Chemico-Technological Journal. 12 (2010), H. 2}, journal = {Eurasian Chemico-Technological Journal. 12 (2010), H. 2}, isbn = {1562-3920}, pages = {145 -- 150}, year = {2010}, language = {en} } @article{GossmannFrotscherLinderetal.2016, author = {Goßmann, Matthias and Frotscher, Ralf and Linder, Peter and Bayer, Robin and Epple, U. and Staat, Manfred and Temiz Artmann, Ayseg{\"u}l and Artmann, Gerhard}, title = {Mechano-pharmacological characterization of cardiomyocytes derived from human induced pluripotent stem cells}, series = {Cellular physiology and biochemistry}, volume = {38}, journal = {Cellular physiology and biochemistry}, number = {3}, publisher = {Karger}, address = {Basel}, issn = {1421-9778 (Online)}, doi = {10.1159/000443124}, pages = {1182 -- 1198}, year = {2016}, abstract = {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.}, language = {en} } @techreport{StoelzleFeixThomasEngelstaedteretal.2021, author = {St{\"o}lzle-Feix, Sonja and Thomas, Ulrich and Engelst{\"a}dter, Max and Goßmann, Matthias and Linder, Peter and Staat, Manfred and Raman, Aravind Hariharan and Jung, Alexander and Fertig, Niels}, title = {Plattformtechnologie f{\"u}r kardiale Sicherheitspharmakologie basierend auf teilsynthetischem Herzmuskelgewebe (FLEXcyte) : gemeinsamer FuE-Abschlussbericht aller Partner des Verbundprojektes : Projektlaufzeit: 01.10.2018 bis 30.09.2020}, publisher = {Nanion Technologies GmbH}, address = {M{\"u}nchen}, doi = {10.2314/KXP:1813208581}, pages = {IV, 85 Seiten, 2 ungez{\"a}hlte Seiten}, year = {2021}, language = {de} } @article{KurulganDemirciDemirciLinderetal.2012, author = {Kurulgan Demirci, Eylem and Demirci, Taylan and Linder, Peter and Trzewik, J{\"u}rgen and Gierkowski, Jessica Ricarda and Gossmann, Matthias and Kayser, Peter and Porst, Dariusz and Digel, Ilya and Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l}, title = {rhAPC reduces the endothelial cell permeability via a decrease of contractile tensions induced by endothelial cells}, series = {Journal of Bioscience and Bioengineering}, volume = {113}, journal = {Journal of Bioscience and Bioengineering}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1347-4421}, doi = {10.1016/j.jbiosc.2012.03.019}, pages = {212 -- 219}, year = {2012}, abstract = {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.}, language = {en} } @article{FrotscherMuanghongDursunetal.2016, author = {Frotscher, Ralf and Muanghong, Danita and Dursun, G{\"o}zde and Goßmann, Matthias and Temiz Artmann, Ayseg{\"u}l and Staat, Manfred}, title = {Sample-specific adaption of an improved electro-mechanical model of in vitro cardiac tissue}, series = {Journal of Biomechanics}, volume = {49}, journal = {Journal of Biomechanics}, number = {12}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0021-9290 (Print)}, doi = {10.1016/j.jbiomech.2016.01.039}, pages = {2428 -- 2435}, year = {2016}, abstract = {We present an electromechanically coupled computational model for the investigation of a thin cardiac tissue construct consisting of human-induced pluripotent stem cell-derived atrial, ventricular and sinoatrial cardiomyocytes. The mechanical and electrophysiological parts of the finite element model, as well as their coupling are explained in detail. The model is implemented in the open source finite element code Code_Aster and is employed for the simulation of a thin circular membrane deflected by a monolayer of autonomously beating, circular, thin cardiac tissue. Two cardio-active drugs, S-Bay K8644 and veratridine, are applied in experiments and simulations and are investigated with respect to their chronotropic effects on the tissue. These results demonstrate the potential of coupled micro- and macroscopic electromechanical models of cardiac tissue to be adapted to experimental results at the cellular level. Further model improvements are discussed taking into account experimentally measurable quantities that can easily be extracted from the obtained experimental results. The goal is to estimate the potential to adapt the presented model to sample specific cell cultures.}, language = {en} } @inproceedings{FrotscherGossmannTemizArtmannetal.2013, author = {Frotscher, Ralf and Goßmann, Matthias and Temiz Artmann, Ayseg{\"u}l and Staat, Manfred}, title = {Simulation of cardiac cell-seeded membranes using the edge-based smoothed FEM}, series = {1st International Conference "Shell and Membrane Theories in Mechanics and Biology: From Macro- to Nanoscale Structures", Minsk, Belarus, Sept. 16-20, 2013}, booktitle = {1st International Conference "Shell and Membrane Theories in Mechanics and Biology: From Macro- to Nanoscale Structures", Minsk, Belarus, Sept. 16-20, 2013}, publisher = {Verl. d. Weißruss. Staatl. Univ.}, address = {Minsk}, organization = {International Conference Shell and Membrane Theories in Mechanics and Biology: From Macro- to Nanoscale Structures <1, 2013, Minsk>}, isbn = {978-985-553-135-8}, pages = {165 -- 167}, year = {2013}, language = {en} } @incollection{FrotscherGossmannRaatschenetal.2015, author = {Frotscher, Ralf and Goßmann, Matthias and Raatschen, Hans-J{\"u}rgen and Temiz Artmann, Ayseg{\"u}l and Staat, Manfred}, title = {Simulation of cardiac cell-seeded membranes using the edge-based smoothed FEM}, series = {Shell and membrane theories in mechanics and biology. (Advanced structured materials ; 45)}, booktitle = {Shell and membrane theories in mechanics and biology. (Advanced structured materials ; 45)}, publisher = {Springer}, address = {Heidelberg}, isbn = {978-3-319-02534-6 ; 978-3-319-02535-3}, pages = {187 -- 212}, year = {2015}, abstract = {We present an electromechanically coupled Finite Element model for cardiac tissue. It bases on the mechanical model for cardiac tissue of Hunter et al. that we couple to the McAllister-Noble-Tsien electrophysiological model of purkinje fibre cells. The corresponding system of ordinary differential equations is implemented on the level of the constitutive equations in a geometrically and physically nonlinear version of the so-called edge-based smoothed FEM for plates. Mechanical material parameters are determined from our own pressure-deflection experimental setup. The main purpose of the model is to further examine the experimental results not only on mechanical but also on electrophysiological level down to ion channel gates. Moreover, we present first drug treatment simulations and validate the model with respect to the experiments.}, language = {en} }