Balance of mechanical forces drives endothelial gap formation and may facilitate cancer and immune-cell extravasation
Name
journal.pcbi.1006395.pdf
Description
Published version
Size
2.27 MB
Format
Adobe PDF
Checksum (MD5)
7b65cf9a0ec4f0ea9656beae3d991b4d
Author(s)
Escribano, Jorge
Chen, Michelle B.
Moeendarbary, Emad
Kamm, Roger D.
Spill, Fabian
Date Issued
May 2, 2019
Journal
PloS one
Publisher
Public Library of Science (PLoS)
Citation
Escribano, Jorge et al. "Balance of mechanical forces drives endothelial gap formation and may facilitate cancer and immune-cell extravasation." PloS one 15 (2010): e1006395 © 2019 The Author(s)
Version
Final published version
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 extrava-sate 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.
Subjects
Ecology
Modelling and Simulation
Computational Theory and Mathematics
Genetics
Ecology, Evolution, Behavior and Systematics
Molecular Biology
Cellular and Molecular Neuroscience
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Mechanical Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/journal.pcbi.1006395
