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Tracking single hiPSC-derived cardiomyocyte contractile function using CONTRAX an efficient pipeline for traction force measurement

Author

Listed:
  • Gaspard Pardon

    (School of Engineering and School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine
    University of California)

  • Alison S. Vander Roest

    (School of Engineering and School of Medicine
    Stanford University School of Medicine
    Stanford University School of Medicine
    Michigan Engineering)

  • Orlando Chirikian

    (University of California)

  • Foster Birnbaum

    (Stanford University School of Medicine)

  • Henry Lewis

    (School of Engineering and School of Medicine)

  • Erica A. Castillo

    (School of Engineering and School of Medicine
    University of California)

  • Robin Wilson

    (School of Engineering and School of Medicine)

  • Aleksandra K. Denisin

    (School of Engineering and School of Medicine)

  • Cheavar A. Blair

    (School of Engineering and School of Medicine
    University of California
    University of Kentucky)

  • Colin Holbrook

    (Stanford University School of Medicine)

  • Kassie Koleckar

    (Stanford University School of Medicine)

  • Alex C. Y. Chang

    (Stanford University School of Medicine
    Stanford University School of Medicine
    Shanghai Jiao Tong University School of Medicine
    Stanford University School of Medicine)

  • Helen M. Blau

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Beth L. Pruitt

    (School of Engineering and School of Medicine
    Stanford University School of Medicine
    University of California
    University of California)

Abstract

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time. Three software modules enable: parameter-based identification of single hiPSC-CMs; automated video acquisition of >200 cells/hour; and contractility measurements via traction force microscopy. We analyze >4,500 hiPSC-CMs over time in the same cells under orthogonal conditions of culture media and substrate stiffnesses; +/− drug treatment; +/− cardiac mutations. Using undirected clustering, we reveal converging maturation patterns, quantifiable drug response to Mavacamten and significant deficiencies in hiPSC-CMs with disease mutations. CONTRAX empowers researchers with a potent quantitative approach to develop cardiac therapies.

Suggested Citation

  • Gaspard Pardon & Alison S. Vander Roest & Orlando Chirikian & Foster Birnbaum & Henry Lewis & Erica A. Castillo & Robin Wilson & Aleksandra K. Denisin & Cheavar A. Blair & Colin Holbrook & Kassie Kole, 2024. "Tracking single hiPSC-derived cardiomyocyte contractile function using CONTRAX an efficient pipeline for traction force measurement," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49755-3
    DOI: 10.1038/s41467-024-49755-3
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    References listed on IDEAS

    as
    1. Xin Tang & Alireza Tofangchi & Sandeep V Anand & Taher A Saif, 2014. "A Novel Cell Traction Force Microscopy to Study Multi-Cellular System," PLOS Computational Biology, Public Library of Science, vol. 10(6), pages 1-15, June.
    2. Kacey Ronaldson-Bouchard & Stephen P. Ma & Keith Yeager & Timothy Chen & LouJin Song & Dario Sirabella & Kumi Morikawa & Diogo Teles & Masayuki Yazawa & Gordana Vunjak-Novakovic, 2018. "Advanced maturation of human cardiac tissue grown from pluripotent stem cells," Nature, Nature, vol. 556(7700), pages 239-243, April.
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