UCLA

Microvasculature structures vary drastically from species to species, and from organs to organs. Different structures signify inclinations of distinct blood flow perfusion features: uniform, or localized? Robust, or efficient? Like the vertebrate tissues having preferred types of vasculature systems that emphasize different traits, in the course of my research, I chose two contrasting systems to be studied by virtue of their specific features: mammalian cerebral cortex microvasculature, and zebrafish embryo trunk microvasculature. For mammalian cerebral microvasculature, considering the distinguished hierarchical construction, and the complex, dense nature of the capillary bed perfusing brain tissue, a model that abstracts the structure while revealing the relationship between blood perfusion and network properties would be extremely helpful; in contrast, zebrafish embryo trunk microvasculature is by itself a simple structure, but being an embryo, its hemodynamic features still undergo developments, and the network would adapt accordingly, which provides an excellent model to study microvascular network adaptation.

Specifically, in different mammalian cortices, I found that the dense, parallel penetrating vessels perfusing the cerebral cortex -- arterioles and venules, are consistently in imbalanced ratios. Whether and how the arteriole-venule arrangement and ratio affect the efficiency of energy delivery to the cortex has never been asked before. I show by mathematical modeling and analysis of the mapped mouse sensory cortex that the perfusive efficiency of the network is predicted to be limited by low flow regions produced between pairs of arterioles or pairs of venules. Increasing either arteriole or venule density decreases the size of these low flow regions but increases their number, setting an optimal ratio between arterioles and venules that closely matches that observed across mammalian cortical vasculature. Low flow regions are reshaped in complex ways by changes in vascular conductance, creating geometric challenges for matching cortical perfusion with neuronal activity.

Within the zebrafish trunk, tuning of vessel radii ensures red blood cells are delivered at equal rates across tens of microvessels. How do vessels find optimal radii? Vessels are known to adapt their radii to maintain the shear stress from blood flow at the vessel wall at a set point. Yet models of adaptation purely on the basis of average shear stress have not, until now, been able to produce complex loopy networks that resemble real microvascular systems. The shear stress on real vessel endothelia peaks sharply when a red blood cell passes through the vessel. I show that if vessel shear stress set points are cued to the stress peaks, then stable shear-stress-based adaptation is possible. Model networks that respond to peak stresses alone can quantitatively reproduce the observed zebrafish trunk microvasculature, including its adaptive trajectory when hematocrit changes. My work reveals the potential for mechanotransduction alone to generate stable hydraulically tuned microvascular networks.

When parts of the zebrafish network -- the anastomoses in the distant trunk that connects the artery and the vein directly -- are amputated, a localization of blood flow at the zebrafish tail is observed in my adaptation model, which is verified through experiments. This discovery highlights a specific structure's function, which can only be identified under network adaptation, and shows the significance of taking adaptation into account when evaluating a vascular structure's hemodynamic functions.