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

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.