@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{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{KurulganDemirciDemirciTrzewiketal.2011, author = {Kurulgan Demirci, Eylem and Demirci, T. and Trzewik, J{\"u}rgen and Linder, Peter and Karakulah, G. and Artmann, Gerhard and Sakizli, M. and Temiz Artmann, Ayseg{\"u}l}, title = {Genome-Wide Gene Expression Analysis of NIH 3T3 Cell Line Under Mechanical Stimulation}, series = {Cellular and molecular bioengineering. 4 (2011), H. 1}, journal = {Cellular and molecular bioengineering. 4 (2011), H. 1}, publisher = {Springer}, address = {Berlin}, isbn = {1865-5025}, pages = {46 -- 55}, year = {2011}, 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{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{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{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{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{DigelMaggakisKelemenZerlinetal.2006, author = {Digel, Ilya and Maggakis-Kelemen, Christina and Zerlin, Kay and Linder, Peter}, title = {Body temperature-related structural transitions of monotremal and human hemoglobin}, series = {Biophysical Journal. 91 (2006), H. 8}, journal = {Biophysical Journal. 91 (2006), H. 8}, isbn = {1542-0086}, pages = {3014 -- 3021}, year = {2006}, language = {en} } @article{DigelKurulganDemirciLinderetal.2007, author = {Digel, Ilya and Kurulgan Demirci, Eylem and Linder, Peter and Kayser, Peter}, title = {Decrease in extracellular collagen crosslinking after NMR magnetic field application in skin fibroblasts}, series = {Medical and Biological Engineering and Computing. 45 (2007), H. 1}, journal = {Medical and Biological Engineering and Computing. 45 (2007), H. 1}, isbn = {1741-0444}, pages = {91 -- 97}, year = {2007}, language = {en} }