Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions

Pragati Pandey, William Hawkes, Junquiang Hu, William Valentine Megone, Julien Gautrot, Narayana Anilkumar, Min Zhang, Liisa Hirvonen, Susan Cox, Elisabeth Ehler, James Hone, Michael Sheetz, Thomas Iskratsch

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Mechanical properties are cues for many biological processes in health or disease. In the heart, changes to the extracellular matrix composition and cross-linking result in stiffening of the cellular microenvironment during development. Moreover, myocardial infarction and cardiomyopathies lead to fibrosis and a stiffer environment, affecting cardiomyocyte behavior. Here, we identify that single cardiomyocyte adhesions sense simultaneous (fast oscillating) cardiac and (slow) non-muscle myosin contractions. Together, these lead to oscillating tension on the mechanosensitive adaptor protein talin on substrates with a stiffness of healthy adult heart tissue, compared with no tension on embryonic heart stiffness and continuous stretching on fibrotic stiffness. Moreover, we show that activation of PKC leads to the induction of cardiomyocyte hypertrophy in a stiffness-dependent way, through activation of non-muscle myosin. Finally, PKC and non-muscle myosin are upregulated at the costameres in heart disease, indicating aberrant mechanosensing as a contributing factor to long-term remodeling and heart failure. Pandey et al. identify that cardiomyocytes sense the rigidity of the heart by measuring the combined forces from non-muscle and muscle myosin. This can result in cyclic or continuous stretching of the mechanosensitive protein talin, depending on the substrate stiffness and the level of non-muscle myosin activity.

Original languageEnglish (US)
Pages (from-to)326-336.e3
JournalDevelopmental Cell
Volume44
Issue number3
DOIs
StatePublished - Feb 5 2018
Externally publishedYes

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Keywords

  • actomyosin
  • cardiac myosin
  • cardiomyocyte rigidity sensing
  • contractility
  • FHOD1
  • heart disease
  • non-muscle myosin
  • PKC
  • Src
  • Talin

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

Cite this

Pandey, P., Hawkes, W., Hu, J., Megone, W. V., Gautrot, J., Anilkumar, N., Zhang, M., Hirvonen, L., Cox, S., Ehler, E., Hone, J., Sheetz, M., & Iskratsch, T. (2018). Cardiomyocytes Sense Matrix Rigidity through a Combination of Muscle and Non-muscle Myosin Contractions. Developmental Cell, 44(3), 326-336.e3. https://doi.org/10.1016/j.devcel.2017.12.024