Two-Dimensional Culture Systems to Enable Mechanics-Based Assays for Stem Cell-Derived Cardiomyocytes

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Abstract

Well-controlled 2D cell culture systems advance basic investigations in cell biology and provide innovative platforms for drug development, toxicity testing, and diagnostic assays. These cell culture systems have become more advanced in order to provide and to quantify the appropriate biomechanical and biochemical cues that mimic the milieu of conditions present in vivo. Here we present an innovative 2D cell culture system to investigate human stem cell-derived cardiomyocytes, the muscle cells of the heart responsible for pumping blood throughout the body. We designed our 2D cell culture platform to control intracellular features to produce adult-like cardiomyocyte organization with connectivity and anisotropic conduction comparable to the native heart, and combined it with optical microscopy to quantify cell-cell and cell-substrate mechanical interactions. We show the measurement of forces and displacements that occur within individual cells, between neighboring cells, and between cells and their surrounding matrix. This system has broad potential to expand our understanding of tissue physiology, with particular advantages for the study of the mechanically active heart. Furthermore, this technique should prove valuable in screening potential drugs for efficacy and testing for toxicity.

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Change history

  • 03 January 2020

    The authors would like to correct the sentence ���The mass ratio��������� in the subsection on Engineered Substrate System in MATERIALS AND METHODS, to read:

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Acknowledgements

Research reported in this publication was supported in part by the National Science Foundation under grant number 1660703 (JN) and by the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health under award number R01 HL107367 (JCR). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health or the National Science Foundation. Support was also provided by the Karen Thompson Medhi Professorship (WCC), the Graduate School (WCC) and the Office of the Vice Chancellor for Research and Graduate Education (WCC, JN) at the University of Wisconsin-Madison. Additional thanks are given to Dr. Timothy Kamp of the University of Wisconsin-Madison for providing the cTnT H9 hESC line used in some of the experiments described above.

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Notbohm, J., Napiwocki, B., de Lange, W. et al. Two-Dimensional Culture Systems to Enable Mechanics-Based Assays for Stem Cell-Derived Cardiomyocytes. Exp Mech 59, 1235–1248 (2019). https://doi.org/10.1007/s11340-019-00473-8

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Keywords

  • Cardiomyocyte
  • Cell culture systems
  • Micropatterning
  • Traction force microscopy
  • Digital image correlation