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

Gaspard Pardon1,2,3,4,5, Alison S Vander Roest1,3,6,7, Orlando Chirikian8

  • 1Departments of Mechanical Engineering and of Bioengineering, Stanford University, School of Engineering and School of Medicine, Stanford, CA, USA.

Nature Communications
|June 26, 2024
PubMed

Insights

CONTRAX is a new open-access pipeline for tracking human induced pluripotent stem cell-derived cardiomyocyte (hiPSC-CM) contractility. This tool enables high-throughput analysis of cellular function over time, aiding in cardiomyopathy and cardiotoxicity research.

Area of Science:

  • Biomedical Engineering
  • Stem Cell Biology
  • Cardiovascular Research

Background:

  • Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are crucial in vitro models for studying heart diseases and drug toxicity.
  • High-throughput, time-resolved quantification of hiPSC-CM contractile function is vital for understanding cellular mechanisms impacting heart function.

Purpose of the Study:

  • To introduce CONTRAX, an open-access, versatile pipeline for quantitative tracking of single hiPSC-CM contractile dynamics over time.
  • To provide a streamlined approach for analyzing large numbers of hiPSC-CMs under various experimental conditions.

Main Methods:

  • CONTRAX comprises three software modules for cell identification, automated video acquisition (>200 cells/hour), and contractility measurement using traction force microscopy.
  • Analysis of over 4,500 hiPSC-CMs across different culture media, substrate stiffnesses, drug treatments, and in the presence of cardiac mutations.

Main Results:

  • Undirected clustering revealed consistent hiPSC-CM maturation patterns.
  • Quantifiable drug responses to Mavacamten were observed.
  • Significant functional deficiencies were identified in hiPSC-CMs carrying disease mutations.

Conclusions:

  • CONTRAX offers a powerful quantitative method for analyzing hiPSC-CM contractility.
  • This pipeline can accelerate the development of novel cardiac therapies by providing detailed insights into cellular function and disease mechanisms.