Balance of mechanical forces drives endothelial gap formation and may facilitate cancer and immune-cell extravasation

Research output: Contribution to journalArticle

Authors

  • Jorge Escribano
  • Michelle B. Chen
  • Emad Moeendarbary
  • Xuan Cao
  • Vivek Shenoy
  • Jose Manuel Garcia-Aznar
  • Roger D. Kamm

Colleges, School and Institutes

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.

Bibliographic note

21 pages, 28 supplementary pages, 5 figures, 15 supplementary figures

Details

Original languageEnglish
Article numbere1006395
Pages (from-to)e1006395
JournalPLoS Computational Biology
Volume15
Issue number5
Publication statusPublished - 2 May 2019

Keywords

  • q-bio.CB, physics.bio-ph