The structural and functional maturation of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) is essential for application to pharmaceutical testing, disease modeling, and ultimately therapeutic use. Multicellular 3D-tissue platforms have improved functional maturation of hiPSC-CMs, but probing cardiac contractile properties remains challenging in a 3D environment, especially at depth and in live tissues. Using small angle X-ray scattering (SAXS) images, we show that hiPSC-CMs, matured and examined in a 3D environment, exhibit periodic spatial arrangement of the myofilament lattice, which has not been previously detected in hiPSC-CMs. Contractile force is found to correlate with both scattering intensity (R2=0.44) and lattice spacing (R2=0.46). Scattering intensity also correlates with lattice spacing (R2=0.81), suggestive of lower noise in our structural measurement relative to the functional measurement. Notably, we observe 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.
@article{arxiv.2101.06196,
title = {Probing Subcellular Nanostructure of Engineered Human Cardiomyocytes in 3D Tissue},
author = {Josh Javor and Jourdan K. Ewoldt and Paige E. Cloonan and Anant Chopra and Rebeccah J. Luu and Guillaume Freychet and Mikhail Zhernenkov and Karl Ludwig and Jonathan G. Seidman and Christine E. Seidman and Christopher S. Chen and David J. Bishop},
journal= {arXiv preprint arXiv:2101.06196},
year = {2021}
}
Comments
12 pages, 6 figures, supplementary material available upon request to the lead author