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Crosstalk of cardiomyocytes and fibroblasts in co-cultures

Electromechanical function of cardiac muscle depends critically on the crosstalk of myocytes with non-myocytes. Upon cardiac fibrosis, fibroblasts translocate into infarcted necrotic tissue and alter their communication capabilities. In the present in vitro study, we determined a multiple parameter...

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Autores principales: Rother, J., Richter, C., Turco, L., Knoch, F., Mey, I., Luther, S., Janshoff, A., Bodenschatz, E., Tarantola, M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632504/
https://www.ncbi.nlm.nih.gov/pubmed/26085516
http://dx.doi.org/10.1098/rsob.150038
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author Rother, J.
Richter, C.
Turco, L.
Knoch, F.
Mey, I.
Luther, S.
Janshoff, A.
Bodenschatz, E.
Tarantola, M.
author_facet Rother, J.
Richter, C.
Turco, L.
Knoch, F.
Mey, I.
Luther, S.
Janshoff, A.
Bodenschatz, E.
Tarantola, M.
author_sort Rother, J.
collection PubMed
description Electromechanical function of cardiac muscle depends critically on the crosstalk of myocytes with non-myocytes. Upon cardiac fibrosis, fibroblasts translocate into infarcted necrotic tissue and alter their communication capabilities. In the present in vitro study, we determined a multiple parameter space relevant for fibrotic cardiac tissue development comprising the following essential processes: (i) adhesion to substrates with varying elasticity, (ii) dynamics of contractile function, and (iii) electromechanical connectivity. By combining electric cell-substrate impedance sensing (ECIS) with conventional optical microscopy, we could measure the impact of fibroblast–cardiomyocyte ratio on the aforementioned parameters in a non-invasive fashion. Adhesion to electrodes was quantified via spreading rates derived from impedance changes, period analysis allowed us to measure contraction dynamics and modulations of the barrier resistance served as a measure of connectivity. In summary, we claim that: (i) a preferred window for substrate elasticity around 7 kPa for low fibroblast content exists, which is shifted to stiffer substrates with increasing fibroblast fractions. (ii) Beat frequency decreases nonlinearly with increasing fraction of fibroblasts, while (iii) the intercellular resistance increases with a maximal functional connectivity at 75% fibroblasts. For the first time, cardiac cell–cell junction density-dependent connectivity in co-cultures of cardiomyocytes and fibroblasts was quantified using ECIS.
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spelling pubmed-46325042015-11-05 Crosstalk of cardiomyocytes and fibroblasts in co-cultures Rother, J. Richter, C. Turco, L. Knoch, F. Mey, I. Luther, S. Janshoff, A. Bodenschatz, E. Tarantola, M. Open Biol Research Electromechanical function of cardiac muscle depends critically on the crosstalk of myocytes with non-myocytes. Upon cardiac fibrosis, fibroblasts translocate into infarcted necrotic tissue and alter their communication capabilities. In the present in vitro study, we determined a multiple parameter space relevant for fibrotic cardiac tissue development comprising the following essential processes: (i) adhesion to substrates with varying elasticity, (ii) dynamics of contractile function, and (iii) electromechanical connectivity. By combining electric cell-substrate impedance sensing (ECIS) with conventional optical microscopy, we could measure the impact of fibroblast–cardiomyocyte ratio on the aforementioned parameters in a non-invasive fashion. Adhesion to electrodes was quantified via spreading rates derived from impedance changes, period analysis allowed us to measure contraction dynamics and modulations of the barrier resistance served as a measure of connectivity. In summary, we claim that: (i) a preferred window for substrate elasticity around 7 kPa for low fibroblast content exists, which is shifted to stiffer substrates with increasing fibroblast fractions. (ii) Beat frequency decreases nonlinearly with increasing fraction of fibroblasts, while (iii) the intercellular resistance increases with a maximal functional connectivity at 75% fibroblasts. For the first time, cardiac cell–cell junction density-dependent connectivity in co-cultures of cardiomyocytes and fibroblasts was quantified using ECIS. The Royal Society 2015-06-17 /pmc/articles/PMC4632504/ /pubmed/26085516 http://dx.doi.org/10.1098/rsob.150038 Text en http://creativecommons.org/licenses/by/4.0/ © 2015 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Rother, J.
Richter, C.
Turco, L.
Knoch, F.
Mey, I.
Luther, S.
Janshoff, A.
Bodenschatz, E.
Tarantola, M.
Crosstalk of cardiomyocytes and fibroblasts in co-cultures
title Crosstalk of cardiomyocytes and fibroblasts in co-cultures
title_full Crosstalk of cardiomyocytes and fibroblasts in co-cultures
title_fullStr Crosstalk of cardiomyocytes and fibroblasts in co-cultures
title_full_unstemmed Crosstalk of cardiomyocytes and fibroblasts in co-cultures
title_short Crosstalk of cardiomyocytes and fibroblasts in co-cultures
title_sort crosstalk of cardiomyocytes and fibroblasts in co-cultures
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4632504/
https://www.ncbi.nlm.nih.gov/pubmed/26085516
http://dx.doi.org/10.1098/rsob.150038
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