title: Crosstalk of cardiomyocytes and fibroblasts in co-cultures.
abstract: 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.
authors.affiliation: Institute of Physical Chemistry, University of Goettingen, Tammannstrasse 6, Goettingen 37077, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Rother
authors.affiliation: Research Group Biomedical Physics, Max Planck Institute for Dynamics and Self-Organization (MPIDS), Am Fassberg 17, Goettingen 37077, Germany Heart Research Center Goettingen, Robert-Koch-Strasse 40, Goettingen 37099, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Richter
authors.affiliation: Laboratory for Fluid Dynamics, Pattern Formation and Biocomplexity, Am Fassberg 17, Goettingen 37077, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Turco
authors.affiliation: Laboratory for Fluid Dynamics, Pattern Formation and Biocomplexity, Am Fassberg 17, Goettingen 37077, Germany.
authors.forename: F
authors.initials: F
authors.lastname: Knoch
authors.affiliation: Institute of Organic and Biomolecular Chemistry, Georg-August University, Tammannstrasse 6, Goettingen 37077, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Mey
authors.affiliation: Research Group Biomedical Physics, Max Planck Institute for Dynamics and Self-Organization (MPIDS), Am Fassberg 17, Goettingen 37077, Germany German Center for Cardiovascular Research (DZHK), Oudenarder Strasse 16, Berlin 13347, Germany Heart Research Center Goettingen, Robert-Koch-Strasse 40, Goettingen 37099, Germany Institute of Nonlinear Dynamics, Georg-August University, Friedrich-Hund-Platz 1, Goettingen 37077, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Luther
authors.affiliation: Institute of Physical Chemistry, University of Goettingen, Tammannstrasse 6, Goettingen 37077, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Janshoff
authors.affiliation: Laboratory for Fluid Dynamics, Pattern Formation and Biocomplexity, Am Fassberg 17, Goettingen 37077, Germany German Center for Cardiovascular Research (DZHK), Oudenarder Strasse 16, Berlin 13347, Germany Heart Research Center Goettingen, Robert-Koch-Strasse 40, Goettingen 37099, Germany Institute of Nonlinear Dynamics, Georg-August University, Friedrich-Hund-Platz 1, Goettingen 37077, Germany.
authors.forename: E
authors.initials: E
authors.lastname: Bodenschatz
authors.affiliation: Laboratory for Fluid Dynamics, Pattern Formation and Biocomplexity, Am Fassberg 17, Goettingen 37077, Germany marco.tarantola@ds.mpg.de.
authors.forename: M
authors.initials: M
authors.lastname: Tarantola
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication; D002478:Cells, Cultured; D018920:Coculture Techniques; D017097:Electric Impedance; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D007091:Image Processing, Computer-Assisted / Q000379:methods*; D007124:Immunoenzyme Techniques; D018625:Microscopy, Atomic Force; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
keywords: cardiomyocytes; contractile function; electric cell-substrate impedance sensing; fibroblasts; fibrosis; impedance spectroscopy