FIGURE 2.

Blood flow-driven capillary pruning and splitting: two sides of the same coin. (A) Heterogeneous flow distribution in dynamic microvascular networks results in shear stress gradients (left). As a consequence, lower perfused segments will be selected to regress (*) and highly perfused segments to split (#) in order to redistribute flow in a more efficient manner in the remodeled network (right). (B) Endothelial cells sense the blood flow and shear stress gradients and respond by elongating and aligning in the direction of flow. In the case of pruning, endothelial cells in the regressing segment (left panel) detach from their neighbors (red) during lumen collapse, polarize (Golgi in brown) and migrate toward the region of higher flow in the adjacent vessel (curved arrows). In capillary splitting (right panel), endothelial cells close to shear stress gradient at the bifurcation, reorganize their cytoskeleton (pink), protrude luminal filopodia (red), and polarize (Golgi in brown) and migrate toward the lumen to form the intraluminal pillar; note the area drawn with low blood flow/shear stress at the nascent pillar which could be permissive for filopodia growth and fusion. Heat map colors indicate the predicted/simulated shear stress values in the modeled microvascular network. Straight arrows indicate the flow direction. Adapted from Chen et al. (2012).