Emmanuel LEMICHEZ, Institut Pasteur, Paris

  • Le 25 janvier 2019
    Institut de Recherche en Santé - 8 quai Moncousu - Nantes
    Amphithéâtre Denis Escande
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  • 11h30

Endothelium breaching by toxins inducing cellular dewetting phenomenon

Endothelium breaching by toxins inducing cellular dewetting phenomenon

Emmanuel LEMICHEZ, invited by Gervaise Loirand (Eq III)
Directeur de Recherche, INSERM, DR1, Directeur du laboratoire des Toxines Bactériennes, Département de Microbiologie, Institut Pasteur, Paris


Several bacterial pathogens compromise the barrier function of endothelia by triggering the opening of transendothelial cell macroaperture (TEM) tunnels as large as several micrometers in width. This phenomenon has been linked to the dissemination of Staphylococcus aureus via the hematogenous 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.

Mis à jour le 31 juillet 2019.