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

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 Koleckar; Alex C. Y. Chang; Helen M. Blau; Beth L. Pruitt

doi:10.1038/s41467-024-49755-3

Nature Communications (Jun 2024)

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

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 Koleckar,
Alex C. Y. Chang,
Helen M. Blau,
Beth L. Pruitt

Affiliations

Gaspard Pardon: Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine
Alison S. Vander Roest: Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine
Orlando Chirikian: Biomolecular Science and Engineering Program, University of California
Foster Birnbaum: Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine
Henry Lewis: Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine
Erica A. Castillo: Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine
Robin Wilson: Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine
Aleksandra K. Denisin: Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine
Cheavar A. Blair: Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine
Colin Holbrook: Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine
Kassie Koleckar: Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine
Alex C. Y. Chang: Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine
Helen M. Blau: Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine
Beth L. Pruitt: Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine

DOI: https://doi.org/10.1038/s41467-024-49755-3
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 19

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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