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 and Beth L. Pruitt ()
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Gaspard Pardon: School of Engineering and School of Medicine
Alison S. Vander Roest: School of Engineering and School of Medicine
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
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
Colin Holbrook: Stanford University School of Medicine
Kassie Koleckar: Stanford University School of Medicine
Alex C. Y. Chang: Stanford University School of Medicine
Helen M. Blau: Stanford University School of Medicine
Beth L. Pruitt: School of Engineering and School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-49755-3

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