Physiologic biomechanics enhance reproducible contractile development in a stem cell derived cardiac muscle platform

Yao-Chang Tsan, Samuel J. DePalma, Yan-Ting Zhao, Adela Capilnasiu, Yu-Wei Wu, Brynn Elder, Isabella Panse, Kathryn Ufford, Daniel L. Matera, Sabrina Friedline, Thomas S. O’Leary, Nadab Wubshet, Kenneth K. Y. Ho, Michael J. Previs, David Nordsletten, Lori L. Isom, Brendon M. Baker, Allen P. Liu and Adam S. Helms ()
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Yao-Chang Tsan: University of Michigan
Samuel J. DePalma: University of Michigan
Yan-Ting Zhao: University of Michigan
Adela Capilnasiu: University of Michigan
Yu-Wei Wu: Academia Sinica
Brynn Elder: University of Michigan
Isabella Panse: University of Michigan
Kathryn Ufford: University of Michigan
Daniel L. Matera: University of Michigan
Sabrina Friedline: University of Michigan
Thomas S. O’Leary: University of Vermont
Nadab Wubshet: University of Michigan
Kenneth K. Y. Ho: University of Michigan
Michael J. Previs: University of Vermont
David Nordsletten: University of Michigan
Lori L. Isom: University of Michigan
Brendon M. Baker: University of Michigan
Allen P. Liu: University of Michigan
Adam S. Helms: University of Michigan

Nature Communications, 2021, vol. 12, issue 1, 1-16

Abstract: Abstract Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) allow investigations in a human cardiac model system, but disorganized mechanics and immaturity of hPSC-CMs on standard two-dimensional surfaces have been hurdles. Here, we developed a platform of micron-scale cardiac muscle bundles to control biomechanics in arrays of thousands of purified, independently contracting cardiac muscle strips on two-dimensional elastomer substrates with far greater throughput than single cell methods. By defining geometry and workload in this reductionist platform, we show that myofibrillar alignment and auxotonic contractions at physiologic workload drive maturation of contractile function, calcium handling, and electrophysiology. Using transcriptomics, reporter hPSC-CMs, and quantitative immunofluorescence, these cardiac muscle bundles can be used to parse orthogonal cues in early development, including contractile force, calcium load, and metabolic signals. Additionally, the resultant organized biomechanics facilitates automated extraction of contractile kinetics from brightfield microscopy imaging, increasing the accessibility, reproducibility, and throughput of pharmacologic testing and cardiomyopathy disease modeling.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26496-1

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DOI: 10.1038/s41467-021-26496-1

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