@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} } @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{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{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{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} } @article{KowalskiLinderZierkeetal.2016, author = {Kowalski, Julia and Linder, Peter and Zierke, S. and Wulfen, B. van and Clemens, J. and Konstantinidis, K. and Ameres, G. and Hoffmann, R. and Mikucki, J. and Tulaczyk, S. and Funke, O. and Blandfort, D. and Espe, Clemens and Feldmann, Marco and Francke, Gero and Hiecker, S. and Plescher, Engelbert and Sch{\"o}ngarth, Sarah and Dachwald, Bernd and Digel, Ilya and Artmann, Gerhard and Eliseev, D. and Heinen, D. and Scholz, F. and Wiebusch, C. and Macht, S. and Bestmann, U. and Reineking, T. and Zetzsche, C. and Schill, K. and F{\"o}rstner, R. and Niedermeier, H. and Szumski, A. and Eissfeller, B. and Naumann, U. and Helbing, K.}, title = {Navigation technology for exploration of glacier ice with maneuverable melting probes}, series = {Cold Regions Science and Technology}, journal = {Cold Regions Science and Technology}, number = {123}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0165-232X}, doi = {10.1016/j.coldregions.2015.11.006}, pages = {53 -- 70}, year = {2016}, abstract = {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.}, language = {en} } @article{MiciliValterOflazetal.2013, author = {Micili, Serap C. and Valter, Markus and Oflaz, Hakan and Ozogul, Candan and Linder, Peter and F{\"o}ckler, Nicole and Artmann, Gerhard and Digel, Ilya and Temiz Artmann, Ayseg{\"u}l}, title = {Optical coherence tomography : a potential tool to predict premature rupture of fetal membranes}, series = {Proceedings of the Institution of Mechanical Engineers. Part H : Journal of engineering in medicine}, volume = {Vol. 227}, journal = {Proceedings of the Institution of Mechanical Engineers. Part H : Journal of engineering in medicine}, number = {No. 4}, publisher = {Sage}, address = {London}, issn = {0046-2039 (Print) ; 2041-3033 (E-Journal)}, pages = {393 -- 401}, year = {2013}, language = {en} } @article{DigelDachwaldArtmannetal.2009, author = {Digel, Ilya and Dachwald, Bernd and Artmann, Gerhard and Linder, Peter and Funke, O.}, title = {A concept of a probe for particle analysis and life detection in icy environments}, pages = {1 -- 24}, year = {2009}, language = {en} } @article{KurulganDemirciLinderDemircietal.2009, author = {Kurulgan Demirci, Eylem and Linder, Peter and Demirci, Taylan and Trzewik, J{\"u}rgen and Digel, Ilya and Artmann, Gerhard and Temiz Artmann, Ayseg{\"u}l}, title = {Contractile tension of endothelial cells: An LPS based in-vitro sepsis model}, series = {IUBMB Life. 61 (2009), H. 3}, journal = {IUBMB Life. 61 (2009), H. 3}, publisher = {Wiley}, address = {Weinheim}, isbn = {1521-6543}, pages = {307 -- 308}, year = {2009}, language = {en} } @article{ArtmannDigelLinderetal.2008, author = {Artmann, Gerhard and Digel, Ilya and Linder, Peter and Porst, Dariusz}, title = {Mechanism of haemoglobin sensing body temperature}, series = {Tissue Engineering Part A. 14 (2008), H. 5}, journal = {Tissue Engineering Part A. 14 (2008), H. 5}, isbn = {1937-3341}, pages = {754 -- 754}, year = {2008}, language = {en} }