Fluid mechanics of the zebrafish embryonic heart trabeculation

Embryonic heart development is a mechanosensitive process, where specific fluid forces are needed for the correct development, and abnormal mechanical stimuli can lead to malformations. It is thus important to understand the nature of embryonic heart fluid forces. However, the fluid dynamical behaviour close to the embryonic endocardial surface is very sensitive to the geometry and motion dynamics of fine-scale cardiac trabecular surface structures. Here, we conducted image-based computational fluid dynamics (CFD) simulations to quantify the fluid mechanics associated with the zebrafish embryonic heart trabeculae. To capture trabecular geometric and motion details, we used a fish line that expresses fluorescence at the endocardial cell membrane, and high resolution 3D confocal microscopy. Our endocardial wall shear stress (WSS) results were found to exceed those reported in existing literature, which were estimated using myocardial rather than endocardial boundaries. By conducting simulations of single intra-trabecular spaces under varied scenarios, where the translational or deformational motions (caused by contraction) were removed, we found that a squeeze flow effect was responsible for most of the WSS magnitude in the intra-trabecular spaces, rather than the shear interaction with the flow in the main ventricular chamber. We found that trabecular structures were responsible for the high spatial variability of the magnitude and oscillatory nature of WSS, and for reducing the endocardial deformational burden. We further found cells attached to the endocardium within the intra-trabecular spaces, which were likely embryonic hemogenic cells, whose presence increased endocardial WSS. Overall, our results suggested that a complex multi-component consideration of both anatomic features and motion dynamics were needed to quantify the trabeculated embryonic heart fluid mechanics. Author summary In the embryonic heart, the mechanical forces that blood fluid imposes on the cardiac tissues are known to be important biological stimuli that affect the proper heart development. We thus perform careful quantification of these forces, using the zebrafish embryo as a model. To do this, we perform high resolution imaging of zebrafish embryonic hearts and image-based flow simulations. We find that the use of a particular fish line that expresses fluorescence at the exact boundary between heart tissue and blood, that is the endocardial cell membrane boundary, is important to give high quality results. The heart's inner surface has uneven trabeculation structures. We find that they cause fluid forces to have spatial variability and an oscillatory nature. We also find that there is a squeezing motion of cardiac tissues on the trabeculation fluid spaces, which is the main mechanism that generated fluid forces. Fluid forces are also affected by a number of cardiac cells that were developing into blood cells, lodged in the trabeculation fluid spaces. Our investigations provide an understanding of the complexity of the fluid forces on the inner surface of the embryonic heart, and our quantifications will be useful to future studies on the biology elicited by these fluid forces.

Automated summary

In this study, the researchers focused on understanding the fluid mechanics associated with embryonic heart trabeculae in zebrafish. They used image-based computational fluid dynamics (CFD) simulations to quantify the fluid dynamics and found that the endocardial wall shear stress (WSS) exceeded previous estimations reported in the literature. They also discovered that a squeeze flow effect within the intra-trabecular spaces accounted for most of the WSS magnitude, rather than the shear interaction with the flow in the main ventricular chamber. The trabecular structures were found to be responsible for the high spatial variability and oscillatory nature of WSS. Additionally, they identified the presence of embryonic hemogenic cells within the intra-trabecular spaces, which increased the endocardial WSS. These findings highlight the complexity of embryonic heart fluid mechanics and provide valuable insights for future studies on the biological effects of these fluid forces.