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Müller, Dominik [VerfasserIn]; Donath, Sören [VerfasserIn]; Brückner, Emanuel Georg [VerfasserIn]; Biswanath Devadas, Santoshi [VerfasserIn]; Daniel, Fiene [VerfasserIn]; Gentemann, Lara [VerfasserIn]; Zweigerdt, Robert [VerfasserIn]; Heisterkamp, Alexander [VerfasserIn]; Kalies, Stefan Michael Klaus [VerfasserIn]

How Localized Z-Disc Damage Affects Force Generation and Gene Expression in Cardiomyocytes - [published Version]

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  • Medientyp: E-Artikel; Sonstige Veröffentlichung
  • Titel: How Localized Z-Disc Damage Affects Force Generation and Gene Expression in Cardiomyocytes
  • Beteiligte: Müller, Dominik [VerfasserIn]; Donath, Sören [VerfasserIn]; Brückner, Emanuel Georg [VerfasserIn]; Biswanath Devadas, Santoshi [VerfasserIn]; Daniel, Fiene [VerfasserIn]; Gentemann, Lara [VerfasserIn]; Zweigerdt, Robert [VerfasserIn]; Heisterkamp, Alexander [VerfasserIn]; Kalies, Stefan Michael Klaus [VerfasserIn]
  • Erschienen: Basel : MDPI, 2021
  • Erschienen in: Bioengineering 8 (2021), Nr. 12 ; Bioengineering
  • Ausgabe: published Version
  • Sprache: Englisch
  • DOI: https://doi.org/10.15488/14202; https://doi.org/10.3390/bioengineering8120213
  • Schlagwörter: Z-disc ; Cardiomyocyte ; Femtosecond laser manipulation ; Traction forces
  • Entstehung:
  • Anmerkungen: Diese Datenquelle enthält auch Bestandsnachweise, die nicht zu einem Volltext führen.
  • Beschreibung: The proper function of cardiomyocytes (CMs) is highly related to the Z-disc, which has a pivotal role in orchestrating the sarcomeric cytoskeletal function. To better understand Z-disc related cardiomyopathies, novel models of Z-disc damage have to be developed. Human pluripotent stem cell (hPSC)-derived CMs can serve as an in vitro model to better understand the sarcomeric cytoskeleton. A femtosecond laser system can be applied for localized and defined damage application within cells as single Z-discs can be removed. We have investigated the changes in force generation via traction force microscopy, and in gene expression after Z-disc manipulation in hPSC-derived CMs. We observed a significant weakening of force generation after removal of a Z-disc. However, no significant changes of the number of contractions after manipulation were detected. The stress related gene NF-kB was significantly upregulated. Additionally, α-actinin (ACTN2) and filamin-C (FLNc) were upregulated, pointing to remodeling of the Z-disc and the sarcomeric cytoskeleton. Ultimately, cardiac troponin I (TNNI3) and cardiac muscle troponin T (TNNT2) were significantly downregulated. Our results allow a better understanding of transcriptional coupling of Z-disc damage and the relation of damage to force generation and can therefore finally pave the way to novel therapies of sarcomeric disorders.
  • Zugangsstatus: Freier Zugang