Mechanics of cardiomyocyte nuclei in a beating heart

How the nucleus, one of the stiffest organelles inside a cell, sustains and responds to mechanical forces in vivo remains understudied. The developing zebrafish vertebrate heart is a unique model system to address this fundamental problem as it generates and withstands substantial mechanical forces.

Using in toto imaging, 3D morphometrics, genetics, pharmacological perturbations and scRNA-seq, our work reveals that the two heart chambers, ventricle and atrium, have strikingly distinct cardiomyocyte nuclear morphologies, possibly correlating with Lamin A/C expression and microtubule localisation. Manipulation of cardiac forces and knockdown of Lamin A/C affects only ventricle nuclear morphology while microtubule manipulation affects nuclear morphology in both chambers. Of note, overexpressing Lamin A/C in atrium, which naturally lacks Lamin A/C expression leads to nuclear fragmentation. Together, these results indicate that the two chambers have distinct nuclear mechanics, possibly reflecting the underlying difference in the biomechanical environment.

Poster presented as part of the Crick BioImage Analysis Symposium 2024.

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