Escribano, J;
Chen, MB;
Moeendarbary, E;
Cao, X;
Shenoy, V;
Garcia-Aznar, JM;
Kamm, RD;
(2019)
Balance of mechanical forces drives endothelial gap formation and may facilitate cancer and immune-cell extravasation.
PLOS Computational Biology
, 15
(5)
, Article e1006395. 10.1371/journal.pcbi.1006395.
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Abstract
The formation of gaps in the endothelium is a crucial process underlying both cancer and immune cell extravasation, contributing to the functioning of the immune system during infection, the unfavorable development of chronic inflammation and tumor metastasis. Here, we present a stochastic-mechanical multiscale model of an endothelial cell monolayer and show that the dynamic nature of the endothelium leads to spontaneous gap formation, even without intervention from the transmigrating cells. These gaps preferentially appear at the vertices between three endothelial cells, as opposed to the border between two cells. We quantify the frequency and lifetime of these gaps, and validate our predictions experimentally. Interestingly, we find experimentally that cancer cells also preferentially extravasate at vertices, even when they first arrest on borders. This suggests that extravasating cells, rather than initially signaling to the endothelium, might exploit the autonomously forming gaps in the endothelium to initiate transmigration.
| Type: | Article |
|---|---|
| Title: | Balance of mechanical forces drives endothelial gap formation and may facilitate cancer and immune-cell extravasation |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1371/journal.pcbi.1006395 |
| Publisher version: | https://doi.org/10.1371/journal.pcbi.1006395 |
| Language: | English |
| Additional information: | Copyright © 2019 Escribano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Keywords: | Stiffness, Cell membranes, Endothelial cells, Endothelium, Bending, Mechanical properties, Cadherins, Mechanical stress |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Mechanical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10074184 |
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