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© Emmanuel Lemichez
Microscopy image showing the formation of large tunnels in a blood vessel endothelial cell induced by a group of bacterial toxins
Publication : Molecular biology of the cell

Force-induced transcellular tunnel formation in endothelial cells

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Molecular biology of the cell - 09 Aug 2017

Ng WP, Webster KD, Stefani C, Schmid EM, Lemichez E, Bassereau P, Fletcher DA

Link to Pubmed [PMID] – 28794268

Mol. Biol. Cell 2017 Aug;

The endothelium serves as a protective semipermeable barrier in blood vessels and lymphatic vessels. Leukocytes and pathogens can pass directly through the endothelium by opening holes in endothelial cells, known as transcellular tunnels, which are formed by contact and self-fusion of the apical and basal plasma membranes. Here we test the hypothesis that the actin cytoskeleton is the primary barrier to transcellular tunnel formation using a combination of atomic force microscopy and fluorescence microscopy of live cells. We find that localized mechanical forces are sufficient to induce the formation of transcellular tunnels in HUVECs. When HUVECs are exposed to the bacterial toxin EDIN, which can induce spontaneous transcellular tunnels, less mechanical work is required to form tunnels due to the reduced cytoskeletal stiffness and thickness of these cells, similar to the effects of a ROCK inhibitor. We also observe actin enrichment in response to mechanical indentation that is reduced in cells exposed to the bacterial toxin. Our study shows that the actin cytoskeleton of endothelial cells provides both passive and active resistance against transcellular tunnel formation, serving as a mechanical barrier that can be overcome by mechanical force as well as disruption of the cytoskeleton.

https://www.ncbi.nlm.nih.gov/pubmed/28794268