Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes

Jan David Kijlstra, Dongjian Hu, Nikhil Mittal, Eduardo Kausel, Peter van der Meer, Arman Garakani, Ibrahim J. Domian*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

34 Citations (Scopus)
201 Downloads (Pure)

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.

Original languageEnglish
Pages (from-to)1226-1238
Number of pages13
JournalStem Cell Reports
Volume5
Issue number6
DOIs
Publication statusPublished - 8-Dec-2015

Keywords

  • MYOCYTE SHAPE
  • CARDIOTOXICITY
  • HEART
  • MODULATION
  • DYNAMICS
  • PLATFORM
  • VOLTAGE

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