Transendothelial migration induces differential migration dynamics of leukocytes in tissue matrix

Abraham C.I. Van Steen, Lanette Kempers, Rouven Schoppmeyer, Max Blokker, David J. Beebe, Martijn A. Nolte, Jaap D. Van Buul*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Leukocyte extravasation into inflamed tissue is a complex process that is difficult to capture as a whole in vitro. We employed a bloodvessel- on-a-chip model in which human endothelial cells were cultured in a tube-like lumen in a collagen-1 matrix. The vessels are leak tight, creating a barrier for molecules and leukocytes. Addition of inflammatory cytokine TNF-α (also known as TNF) caused vasoconstriction, actin remodelling and upregulation of ICAM-1. Introducing leukocytes into the vessels allowed real-time visualization of all different steps of the leukocyte transmigration cascade, including migration into the extracellular matrix. Individual cell tracking over time distinguished striking differences in migratory behaviour between T-cells and neutrophils. Neutrophils cross the endothelial layer more efficiently than T-cells, but, upon entering the matrix, neutrophils display high speed but low persistence, whereas T-cells migrate with low speed and rather linear migration. In conclusion, 3D imaging in real time of leukocyte extravasation in a vessel-on-a-chip enables detailed qualitative and quantitative analysis of different stages of the full leukocyte extravasation process in a single assay.

Original languageEnglish
Article numberjcs258690
Pages (from-to)1-14
Number of pages14
JournalJournal of cell science
Issue number21
Publication statusPublished - 4 Nov 2021

Bibliographical note

Funding Information:
This work was supported by grants from the Landsteiner Foundation for Blood Transfusion Research [1649 to A.C.I.v.S.; 1820 to L.K.], the National Institutes of Health [R01AI134749, R33CA225281 and P30CA014520 to D.J.B.] and ZonMW [NWO Vici grant 91819632 to J.D.v.B.]. Deposited in PMC for release after 12 months.

Publisher Copyright:
© 2021 Company of Biologists Ltd. All rights reserved.


  • Blood vessels
  • Blood-vessel-on-a-chip
  • Endothelial cells
  • Extracellular matrix
  • Inflammation
  • Leukocyte transendothelial migration
  • Migration dynamics
  • Physiological hydrogel
  • Tissue


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