Role of tissue biomechanics in the formation and function of myocardial trabeculae in zebrafish embryos

Cardiac trabeculae are uneven ventricular muscular structures that develop during early embryonic heart development at the outer curvature of the ventricle. Their biomechanical function is not completely understood, and while their formation is known to be mechanosensitive, it is unclear whether ventricular tissue internal stresses play an important role in their formation. Here, we performed imaging and image-based cardiac biomechanics simulations on zebrafish embryonic ventricles to investigate these issues. Microscopy-based ventricular strain measurements show that the appearance of trabeculae coincided with enhanced deformability of the ventricular wall. Image-based biomechanical simulations reveal that the presence of trabeculae reduces ventricular tissue internal stresses, likely acting as structural support in response to the geometry of the ventricle. Passive ventricular pressure-loading experiments further reveal that the formation of trabeculae is associated with a spatial homogenization of ventricular tissue stiffnesses in healthy hearts, but gata1 morphants with a disrupted trabeculation process retain a spatial stiffness heterogeneity. Our findings thus suggest that modulating ventricular wall deformability, stresses, and stiffness are among the biomechanical functions of trabeculae. Further, experiments with gata1 morphants reveal that a reduction in fluid pressures and consequently ventricular tissue internal stresses can disrupt trabeculation, but a subsequent restoration of ventricular tissue internal stresses via vasopressin rescues trabeculation, demonstrating that tissue stresses are important to trabeculae formation. Overall, we find that tissue biomechanics is important to the formation and function of embryonic heart trabeculation. KEY POINTS: Trabeculations are fascinating and important cardiac structures and their abnormalities are linked to embryonic demise. However, their function in the heart and their mechanobiological formation processes are not completely understood. Our imaging and modelling show that tissue biomechanics is the key here. We find that trabeculations enhance cardiac wall deformability, reduce fluid pressure stresses, homogenize wall stiffness, and have alignments that are optimal for providing load-bearing structural support for the heart. We further discover that high ventricular tissue internal stresses consequent to high fluid pressures are needed for trabeculation formation through a rescue experiment, demonstrating that myocardial tissue stresses are as important as fluid flow wall shear stresses for trabeculation formation.