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

Escribano, J. ; Chen, M.B. ; Moeendarbary, E. ; Cao, X. ; Shenoy, V. ; Garcia-Aznar, J.M. (Universidad de Zaragoza) ; Kamm, R.D. ; Spill, F.

Resumen: 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.

Idioma: Inglés

DOI: 10.1371/journal.pcbi.1006395

Año: 2019

Publicado en: PLoS computational biology 15, 5 (2019), [15 pp]
ISSN: 1553-7358

Factor impacto JCR: 4.7 (2019)

Categ. JCR: MATHEMATICAL & COMPUTATIONAL BIOLOGY rank: 6 / 59 = 0.102 (2019) - Q1 - T1
Categ. JCR: BIOCHEMICAL RESEARCH METHODS rank: 9 / 77 = 0.117 (2019) - Q1 - T1

Factor impacto SCIMAGO: 2.91 - Cellular and Molecular Neuroscience (Q1) - Computational Theory and Mathematics (Q1) - Ecology (Q1) - Molecular Biology (Q1) - Genetics (Q1) - Modeling and Simulation (Q1) - Ecology, Evolution, Behavior and Systematics (Q1)

Financiación: info:eu-repo/grantAgreement/EUR/ERC/INSILICO-CELL-ERC-2012-StG-306571
Financiación: info:eu-repo/grantAgreement/ES/MINECO/BES-2013-063684-FPI
Financiación: info:eu-repo/grantAgreement/ES/MINECO/DPI2015-64221-C2-1-R

Tipo y forma: Article (Published version)

Área (Departamento): Área Mec.Med.Cont. y Teor.Est. (Dpto. Ingeniería Mecánica)