Endothelial tissue remodeling induced by intraluminal pressure enhances paracellular solute transport

Jean Cacheux; Aurélien Bancaud; Daniel Alcaide; Jun-Ichi Suehiro; Yoshihiro Akimoto; Hiroyuki Sakurai; Yukiko T Matsunaga

doi:10.1016/j.isci.2023.107141

Endothelial tissue remodeling induced by intraluminal pressure enhances paracellular solute transport

iScience. 2023 Jun 15;26(7):107141. doi: 10.1016/j.isci.2023.107141. eCollection 2023 Jul 21.

Authors

Jean Cacheux^{1

2}, Aurélien Bancaud^{1

2

3}, Daniel Alcaide¹, Jun-Ichi Suehiro⁴, Yoshihiro Akimoto⁵, Hiroyuki Sakurai⁴, Yukiko T Matsunaga^{1

2}

Affiliations

¹ Institute of Industrial Science, The University of Tokyo, Tokyo 153-8505, Japan.
² LIMMS, CNRS-IIS UMI 2820, The University of Tokyo, Tokyo 153-8505, Japan.
³ CNRS, LAAS, 7 Avenue Du Colonel Roche, 31400 Toulouse, France.
⁴ Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, Japan.
⁵ Department of Anatomy, Kyorin University School of Medicine, Mitaka, Tokyo 181-8611, Japan.

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. On application of an intraluminal pressure of 100 Pa, we demonstrate that the flow through the tissue increases by 2.35 times. 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.

Keywords: Bioengineering; Biomechanics; Cell biology; Computer modeling; Tissue engineering.