No abstract

The endothelial layers of the microvasculature regulate the transport of solutes to the surrounding tissues. It remains unclear how this barrier function is affected by blood flow-induced intraluminal pressure. Using a 3D microvessel model, we compare the transport of macromolecules through endothelial tissues at mechanical rest or with intraluminal pressure, and correlate these data with electron microscopy of endothelial junctions. Upon application of an intraluminal pressure of 100 Pa, we demonstrate that the flow through the tissue increases by 135%. This increase is associated with a 25% expansion of microvessel diameter, which leads to tissue remodeling and thinning of the paracellular junctions. We recapitulate these data with the deformable monopore model, in which the increase in paracellular transport is explained by the augmentation of the diffusion rate across thinned junctions under mechanical stress. We therefore suggest that the deformation of microvasculatures contributes to regulate their barrier function.

The Starling principle describes exchanges between blood and tissues based on the balance of hydrostatic and osmotic flows. However, the permeation properties of the main constituent of tissues, namely, collagen, in response to the stress exerted by blood pressure remain poorly characterized. Here, we develop an instrument to determine the elasticity and permeability of collagen gels under tensile and compressive stress based on measuring the temporal change in pressure in an air cavity sealed at the outlet of a collagen slab. Data analysis with an analytical model reveals a drop in the permeability and enhanced strain stiffening of native collagen gels under compression versus tension, both effects being essentially lost after chemical cross-linking. Furthermore, we report the control of the permeability of native collagen gels using sinusoidal fluid injection, an effect explained by the asymmetric response in tension and compression. We lastly suggest that blood-associated pulsations could contribute to exchanges within tissues.

Overview of the output and limitations of modern brain solute transport studies to search for key parameters comparable across experimental setups on both in vivo and in vitro studies.