Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes
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) th...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier
2016
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| Online Access: | http://hdl.handle.net/1721.1/100811 |
| _version_ | 1826209142512025600 |
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| author | Kijlstra, Jan David Hu, Dongjian Mittal, Nikhil van der Meer, Peter Garakani, Arman Domian, Ibrahim J. Kausel, Eduardo A. |
| author2 | Massachusetts Institute of Technology. Department of Civil and Environmental Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Kijlstra, Jan David Hu, Dongjian Mittal, Nikhil van der Meer, Peter Garakani, Arman Domian, Ibrahim J. Kausel, Eduardo A. |
| author_sort | Kijlstra, Jan David |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T14:18:13Z |
| format | Article |
| id | mit-1721.1/100811 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:18:13Z |
| publishDate | 2016 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1008112022-10-01T20:28:25Z Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes Kijlstra, Jan David Hu, Dongjian Mittal, Nikhil van der Meer, Peter Garakani, Arman Domian, Ibrahim J. Kausel, Eduardo A. Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Kausel, Eduardo A. 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. National Heart, Lung, and Blood Institute (Grant U01HL100408-01) National Heart, Lung, and Blood Institute (Grant 1K08 HL091209) Dutch Heart Foundation (Grant 2013SB013) 2016-01-13T17:24:00Z 2016-01-13T17:24:00Z 2015-11 2015-10 Article http://purl.org/eprint/type/JournalArticle 22136711 http://hdl.handle.net/1721.1/100811 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. en_US http://dx.doi.org/10.1016/j.stemcr.2015.10.017 Stem Cell Reports Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier Elsevier |
| spellingShingle | Kijlstra, Jan David Hu, Dongjian Mittal, Nikhil van der Meer, Peter Garakani, Arman Domian, Ibrahim J. Kausel, Eduardo A. Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes |
| title | Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes |
| title_full | Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes |
| title_fullStr | Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes |
| title_full_unstemmed | Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes |
| title_short | Integrated Analysis of Contractile Kinetics, Force Generation, and Electrical Activity in Single Human Stem Cell-Derived Cardiomyocytes |
| title_sort | integrated analysis of contractile kinetics force generation and electrical activity in single human stem cell derived cardiomyocytes |
| url | http://hdl.handle.net/1721.1/100811 |
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