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Project #12853
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#12853 : Impact des contraintes biomécanistiques sur la dynamique des macro-ouverture induits par l’EDIN de Staphylococcus aureus.
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Name of Applicant : Camille MOREL
Date of application : 15-01-2019
Unit : Bacterial Toxins
Location : Calmette gauche – 62 – 1st Floor
Phone : 9485
@ Mail : camille.morel@pasteur.fr
@ PI-Mail : emmanuel.lemichez@pasteur.fr

Project context and summary :

Several bacterial pathogens compromise the barrier function of endothelia by triggering the opening of transendothelial cell macroaperture (TEM) tunnels as large as several micrometres in width. This phenomenon has been linked to the dissemination of Staphylococcus aureus via the haematogenous route. The opening of TEMs occurs in response to the overall relaxation of the actomyosin cytoskeleton and cell spreading-associated with a disruption of focal adhesions via either toxin-induced inhibition of RhoA signaling or increase of the flux of cyclic-AMP broad signaling molecule. The principles of dewetting, i.e. the spontaneous withdrawal of a liquid film from a non-wettable surface by nucleation and growth of dry patches, explain the physical phenomena underpinning the opening of TEM tunnels. For both liquid and cellular dewetting, the growth of holes is governed by a competition between surface forces and line tension that limit the TEM widening. By conducting high-resolution microscopy approaches we unveil the presence of an actomyosin cable encircling TEMs. We have developed a theoretical cellular dewetting framework to interpret TEM physical parameters that are quantitatively determined by laser ablation experiments. We establish the critical role of ezrin and non-muscle myosin II (NMII) in building actin cables along TEM edges to progressively implement line tension that limits TEMs enlargement.


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Project Manager : thomas.obadia@pasteur.fr
Project Type : Short
Status : In Progress


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