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- Title
Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue.
- 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.; Chen, Christopher S.; Bishop, David J.
- 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 (R2 = 0.44) and lattice spacing (R2 = 0.46). The scattering intensity also correlates with lattice spacing (R2 = 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.
- Publication
Microsystems & Nanoengineering, 2021, Vol 7, Issue 1, p1
- ISSN
2096-1030
- Publication type
Article
- DOI
10.1038/s41378-020-00234-x