The Distribution of Fluid Shear Stresses in Capillary Sprouts

Abstract

Fluid shear stress has been implicated as a regulator of sprouting angiogenesis. However, whether endothelial cells within capillary sprouts in vivo experience physiologically relevant shear stresses remains unclear. The objective of our study is to estimate the shear stress distribution along the length of a capillary sprout through computational modeling of blood flow in a blind-ended channel branching off a host vessel. In this model, we use sprout geometries typical for the rat mesenteric microvasculature and consider three types of boundary conditions: (1) a non-permeable vessel wall, (2) a uniformly permeable vessel wall, and (3) a non-permeable vessel wall with open slots (representative of endothelial clefts). Our numerical simulation predicts that for each boundary condition a local maximum shear stress (13.9, 8.9, and 13.3 dyne cm À2 , respectively) occurs at the entrance of a 50 lm long, 6 lm diameter sprout branching at 90°off of a 11 lm diameter host vessel. The shear stress dropped below 0.2 dyne cm À2 , a threshold for endothelial cell activation, within 4.1 lm of the entrance for the non-permeable wall case and 4.2 lm for the uniformly permeable wall case. Shear stress magnitudes within the sprout were above 0.2 dyne cm À2 for longer sprout scenarios and peaked at 5.9 dyne cm À2 at endothelial cell clefts. These results provide a first estimate of relative fluid shear stress magnitudes along a capillary sprout and highlight the importance of investigating endothelial cell responses to flow conditions during angiogenesis in tumors and other altered microenvironments.

The Vital Role of Blood Flow-Induced Proliferation and Migration in Capillary Network Formation in a Multiscale Model of Angiogenesis

“…The level of shear stress for human aorta is 10–20 dyne/cm 2 and for walls of veins is 1–6 dyne/cm 2 [ 23 ]. For single sprouts, wall shear stress is reported to be around 10 dyne/cm 2 or less [ 64 ]. The shear stress has its maximum value in the junction area with parent vessel and decreases along the sprout [ 64 ].…”

“…For single sprouts, wall shear stress is reported to be around 10 dyne/cm 2 or less [ 64 ]. The shear stress has its maximum value in the junction area with parent vessel and decreases along the sprout [ 64 ]. This shear is due to blood flow in parent vessel and leakiness of the newly formed capillaries.…”

Applications of computational models to better understand microvascular remodelling: a focus on biomechanical integration across scales

“…These questions are difficult to answer experimentally because of technical challenges associated with intravital measurement of flow profiles within a sprout. Stapor et al [41] recently used a computational fluid dynamic approach to estimate the shear stress distribution along a blind-ended experimental observations computational models Do hypertensive microvascular networks have increased resistance? Do endothelial cells experience shear stress during capillary sprouting?…”

“…Logically, RBC flow by the entrance of a blind-ended sprout or even within a sprout would impact local shear stress and shear stress gradient magnitudes. Indeed, Stapor et al [41] suggested that RBC flow within a host vessel resulted in local maximum magnitudes at the sprout entrance. RBC plugging of the sprout served to shorten the effective sprout length and similarly influenced magnitudes depending on the wall permeability scenario.…”

Blood flow and endothelial cell phenotype regulation during sprouting angiogenesis

“…ECs are activated by shear stress magnitudes as low as 0.2 dyne/cm 2 [15,69]. Activation means that both integrin and RTK are activated and this does not depend on their specific ligands [1,31]; however, activation of RTK and integrin depends on the activation of VE-cadherin [2].…”