Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue
Date
2021
Authors
Javor, Josh
Ewoldt, Jourdan K.
Cloonan, Paige E.
Chopra, Anant
Luu, Rebeccah J.
Freychet, Guillaume
Zhernenkov, Mikhail
Ludwig, Karl
Seidman, Jonathan G.
Seidman, Christine E.
Version
Published version
OA Version
Citation
J. Javor, J.K. Ewoldt, P.E. Cloonan, A. Chopra, R.J. Luu, G. Freychet, M. Zhernenkov, K. Ludwig, J.G. Seidman, C.E. Seidman, C.S. Chen, D.J. Bishop. 2021. "Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue." Microsystems & Nanoengineering, Volume 7, Issue 1, pp.10-. https://doi.org/10.1038/s41378-020-00234-x
Abstract
The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for pharmaceutical testing, disease modeling, and ultimately therapeutic use. Multicellular 3D-tissue platforms have improved the functional maturation of hiPSC-CMs, but probing cardiac contractile properties in a 3D environment remains challenging, especially at depth and in live tissues. Using small-angle X-ray scattering (SAXS) imaging, we show that hiPSC-CMs matured and examined in a 3D environment exhibit a periodic spatial arrangement of the myofilament lattice, which has not been previously detected in hiPSC-CMs. The contractile force is found to correlate with both the scattering intensity (R 2 = 0.44) and lattice spacing (R 2 = 0.46). The scattering intensity also correlates with lattice spacing (R 2 = 0.81), suggestive of lower noise in our structural measurement than in the functional measurement. Notably, we observed decreased myofilament ordering in tissues with a myofilament mutation known to lead to hypertrophic cardiomyopathy (HCM). Our results highlight the progress of human cardiac tissue engineering and enable unprecedented study of structural maturation in hiPSC-CMs.
Description
License
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