Key result
In engineered human cardiomyocytes, contractile force correlated with myofilament scattering intensity (R2 = 0.44) and lattice spacing (R2 = 0.46), with decreased myofilament ordering observed in tissues with a hypertrophic cardiomyopathy mutation.
Why the study?
Probing cardiac contractile properties in a 3D environment remains challenging, especially at depth and in live tissues, despite multicellular 3D platforms improving hiPSC-CM functional maturation.
Small-angle X-ray scattering (SAXS) imaging enables the detection of periodic spatial arrangement of the myofilament lattice in 3D-engineered hiPSC-CMs, revealing structural differences in a hypertrophic cardiomyopathy model.
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.
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A 2021 study studied Hypertrophic Cardiomyopathy (in vitro model). R403Q myofilament mutation vs. Isogenic wild-type control hiPSC-CMs was evaluated on Correlation of contractile force with myofilament scattering intensity and lattice spacing (R2 = 0.46 for lattice spacing). In engineered human cardiomyocytes, contractile force correlated with myofilament scattering intensity (R2 = 0.44) and lattice spacing (R2 = 0.46), with decreased myofilament ordering observed in tissues with a hypertrophic cardiomyopathy mutation.
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