Microfluidic model of monocyte extravasation reveals the role of hemodynamics and subendothelial matrix mechanics in regulating endothelial integrity

Pérez Rodríguez, S. (Universidad de Zaragoza) ; Huang, S.A. ; Borau, C. (Universidad de Zaragoza) ; García Aznar, J.M. (Universidad de Zaragoza) ; Polacheck, W.J.

Resumen: Extravasation of circulating cells is an essential process that governs tissue inflammation and the body's response to pathogenic infection. To initiate anti-inflammatory and phagocytic functions within tissues, immune cells must cross the vascular endothelial barrier from the vessel lumen to the subluminal extracellular matrix. In this work, we present a microfluidic approach that enables the recreation of a three-dimensional, perfused endothelial vessel formed by human endothelial cells embedded within a collagen-rich matrix. Monocytes are introduced into the vessel perfusate, and we investigate the role of luminal flow and collagen concentration on extravasation. In vessels conditioned with the flow, increased monocyte adhesion to the vascular wall was observed, though fewer monocytes extravasated to the collagen hydrogel. Our results suggest that the lower rates of extravasation are due to the increased vessel integrity and reduced permeability of the endothelial monolayer. We further demonstrate that vascular permeability is a function of collagen hydrogel mass concentration, with increased collagen concentrations leading to elevated vascular permeability and increased extravasation. Collectively, our results demonstrate that extravasation of monocytes is highly regulated by the structural integrity of the endothelial monolayer. The microfluidic approach developed here allows for the dissection of the relative contributions of these cues to further understand the key governing processes that regulate circulating cell extravasation and inflammation.

Idioma: Inglés

DOI: 10.1063/5.0061997

Año: 2021

Publicado en: Biomicrofluidics 15, 5 (2021), 054102 [12 pp.]
ISSN: 1932-1058

Factor impacto JCR: 3.258 (2021)

Categ. JCR: PHYSICS, FLUIDS & PLASMAS rank: 12 / 34 = 0.353 (2021) - Q2 - T2
Categ. JCR: BIOPHYSICS rank: 40 / 72 = 0.556 (2021) - Q3 - T2
Categ. JCR: NANOSCIENCE & NANOTECHNOLOGY rank: 76 / 109 = 0.697 (2021) - Q3 - T3
Categ. JCR: BIOCHEMICAL RESEARCH METHODS rank: 40 / 79 = 0.506 (2021) - Q3 - T2

Factor impacto CITESCORE: 5.5 - Physics and Astronomy (Q1) - Engineering (Q1) - Chemical Engineering (Q2) - Materials Science (Q2)

Factor impacto SCIMAGO: 0.584 - Biomedical Engineering (Q2) - Condensed Matter Physics (Q2) - Genetics (Q2) - Physical and Theoretical Chemistry (Q2) - Molecular Biology (Q2) - Nanoscience and Nanotechnology (Q2) - Materials Science (miscellaneous) (Q2)

Financiación: info:eu-repo/grantAgreement/ES/MEC/FPU16-04398
Financiación: info:eu-repo/grantAgreement/ES/MICINN/RTI2018-094494-B-C21

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Microbiología (Dpto. Microb.Ped.Radio.Sal.Pú.)
Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)