Insights into single hiPSC-derived cardiomyocyte phenotypes and maturation using ConTraX, an efficient pipeline for tracking contractile dynamics
bioRxiv (Cold Spring Harbor Laboratory)(2021)
Abstract
Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in-vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. To understand how cellular mechanisms affect the heart, it is crucial to quantify the contractile function in single hiPSC-CMs over time, however, such measurements remain demanding and low-throughput, and are too seldom considered.
We developed an open-access, versatile, streamlined, and highly automated pipeline to address these challenges and enable quantitative tracking of the contractile dynamics of single hiPSC- CMs over time: ConTraX. Three interlocking software modules enable: (i) parameter-based localization and selection of single hiPSC-CMs; (ii) automated video acquisition of >200 cells/hour; and (iii) streamlined measurements of the contractile parameters via traction force microscopy. Using ConTraX, we analyzed >2,753 hiPSC-CMs over time under orthogonal experimental conditions in terms of culture media and substrate stiffnesses. Using undirected high-dimensional clustering, we dissected the complex diversity of contractile phenotypes in hiPSC-CM populations and revealed converging maturation patterns.
Our modular ConTraX pipeline empowers biologists with a potent quantitative analytic tool applicable to the development of cardiac therapies.
### Competing Interest Statement
The authors have declared no competing interest.
* hiPSC
: Human-induced pluripotent stem cell
CM
: Cardiomyocyte
TFM
: Traction force microscopy
PIV
: Particle image velocimetry
DIC
: Digital image correlation
FTTC
: Fourier transform traction cytometry
GUI
: Graphical User Interface
MoreTranslated text
Key words
cardiomyocyte phenotypes,contrax,contractile dynamics,hipsc-derived
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