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

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 ex

SUBMITTER: Escribano J 

PROVIDER: S-EPMC6497229 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature