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International Journal of Cell Biology
Volume 2012, Article ID 508294, 13 pages
http://dx.doi.org/10.1155/2012/508294
Research Article

Effects of Substrate Mechanics on Contractility of Cardiomyocytes Generated from Human Pluripotent Stem Cells

1Department of Chemical and Biological Engineering, University of Wisconsin-Madison, 1415 Engineering Drive, Madison, WI 53706, USA
2Department of Mechanical Engineering, Cardiovascular Institute and BioX, Stanford University, 496 Lomita Mall, Stanford, CA 94305, USA
3Department of Engineering Physics, University of Wisconsin-Madison, 1500 Engineering Drive, Madison, WI 53706, USA
4Department of Biology, University of Puerto Rico at Cayey, 205 Avenida Antonio R. Barceló, Cayey, PR 00736, USA
5Department of Physiology and Biotechnology and Bioengineering Center, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
6InvivoSciences, 510 Charmany Drive, Madison, WI 53719, USA

Received 20 January 2012; Accepted 23 February 2012

Academic Editor: Adam J. Engler

Copyright © 2012 Laurie B. Hazeltine et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Human pluripotent stem cell (hPSC-) derived cardiomyocytes have potential applications in drug discovery, toxicity testing, developmental studies, and regenerative medicine. Before these cells can be reliably utilized, characterization of their functionality is required to establish their similarity to native cardiomyocytes. We tracked fluorescent beads embedded in 4.4–99.7 kPa polyacrylamide hydrogels beneath contracting neonatal rat cardiomyocytes and cardiomyocytes generated from hPSCs via growth-factor-induced directed differentiation to measure contractile output in response to changes in substrate mechanics. Contraction stress was determined using traction force microscopy, and morphology was characterized by immunocytochemistry for α-actinin and subsequent image analysis. We found that contraction stress of all types of cardiomyocytes increased with substrate stiffness. This effect was not linked to beating rate or morphology. We demonstrated that hPSC-derived cardiomyocyte contractility responded appropriately to isoprenaline and remained stable in culture over a period of 2 months. This study demonstrates that hPSC-derived cardiomyocytes have appropriate functional responses to substrate stiffness and to a pharmaceutical agent, which motivates their use in further applications such as drug evaluation and cardiac therapies.