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Tracking single hiPSC-derived cardiomyocyte contractile function using CONTRAX an efficient pipeline for traction force measurement.
Pardon, Gaspard; Vander Roest, Alison S; Chirikian, Orlando; Birnbaum, Foster; Lewis, Henry; Castillo, Erica A; Wilson, Robin; Denisin, Aleksandra K; Blair, Cheavar A; Holbrook, Colin; Koleckar, Kassie; Chang, Alex C Y; Blau, Helen M; Pruitt, Beth L.
Afiliação
  • Pardon G; Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine, Stanford, CA, USA.
  • Vander Roest AS; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Chirikian O; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Birnbaum F; Departments of Bioengineering and Mechanical Engineering, University of California, Santa Barbara, CA, USA.
  • Lewis H; School of Life Sciences, EPFL École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
  • Castillo EA; Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine, Stanford, CA, USA.
  • Wilson R; Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA.
  • Denisin AK; Department of Pediatrics (Cardiology), Stanford University School of Medicine, Stanford, CA, USA.
  • Blair CA; Department of Biomedical Engineering, Michigan Engineering, University of Michigan Ann Arbor, MI, USA.
  • Holbrook C; Biomolecular Science and Engineering Program, University of California, Santa Barbara, CA, USA.
  • Koleckar K; Baxter Laboratory for Stem Cell Biology, Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, CA, USA.
  • Chang ACY; Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine, Stanford, CA, USA.
  • Blau HM; Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine, Stanford, CA, USA.
  • Pruitt BL; Departments of Bioengineering and Mechanical Engineering, University of California, Santa Barbara, CA, USA.
Nat Commun ; 15(1): 5427, 2024 Jun 26.
Article em En | MEDLINE | ID: mdl-38926342
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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Software / Miócitos Cardíacos / Células-Tronco Pluripotentes Induzidas / Contração Miocárdica Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Software / Miócitos Cardíacos / Células-Tronco Pluripotentes Induzidas / Contração Miocárdica Limite: Humans Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Estados Unidos