Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes
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Kijlstra-2015-Integrated Analysis.pdf
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Author(s)
Kijlstra, Jan David
Hu, Dongjian
Mittal, Nikhil
van der Meer, Peter
Garakani, Arman
Domian, Ibrahim J.
Kausel, Eduardo A.
Date Issued
November 2015
Journal
Stem Cell Reports
Publisher
Elsevier
Citation
Kijlstra, Jan David, Dongjian Hu, Nikhil Mittal, Eduardo Kausel, Peter van der Meer, Arman Garakani, and Ibrahim J. Domian. “Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes.” Stem Cell Reports 5, no. 6 (December 2015): 1226–1238.
Version
Final published version
Abstract
The quantitative analysis of cardiomyocyte function is essential for stem cell-based approaches for the in vitro study of human cardiac physiology and pathophysiology. We present a method to comprehensively assess the function of single human pluripotent stem cell-derived cardiomyocyte (hPSC-CMs) through simultaneous quantitative analysis of contraction kinetics, force generation, and electrical activity. We demonstrate that statistical analysis of movies of contracting hPSC-CMs can be used to quantify changes in cellular morphology over time and compute contractile kinetics. Using a biomechanical model that incorporates substrate stiffness, we calculate cardiomyocyte force generation at single-cell resolution and validate this approach with conventional traction force microscopy. The addition of fluorescent calcium indicators or membrane potential dyes allows the simultaneous analysis of contractility and calcium handling or action potential morphology. Accordingly, our approach has the potential for broad application in the study of cardiac disease, drug discovery, and cardiotoxicity screening.
MIT Department
Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
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DOI of Published Version
https://doi.org/10.1016/j.stemcr.2015.10.017
