  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.
