Probing the subcellular nanostructure of engineered human cardiomyocytes in 3D tissue.
Josh JavorJourdan K EwoldtPaige E CloonanAnant ChopraRebeccah J LuuGuillaume FreychetMikhail ZhernenkovKarl LudwigJonathan G SeidmanChristine E SeidmanChristopher S ChenDavid J BishopPublished in: Microsystems & nanoengineering (2021)
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.
Keyphrases
- endothelial cells
- hypertrophic cardiomyopathy
- high glucose
- left ventricular
- high resolution
- induced pluripotent stem cells
- pluripotent stem cells
- gene expression
- single molecule
- skeletal muscle
- molecular dynamics simulations
- magnetic resonance
- magnetic resonance imaging
- air pollution
- atrial fibrillation
- optical coherence tomography