Caveolae govern plasma membrane mechanics to protect cells against EDIN B-induced transcellular tunnel formation and lethality from S. aureus septicaemia

Camille Morel (1) , Eline Lemerle (2) , Feng-Ching Tsai (3) , Thomas Obadia (4, 5) , Nishit Srivastava (6, 7) , Maud Marechal (1) , Audrey Salles (8) , Marvin Albert (9) , Caroline Stefani (10) , Christophe Lamaze (11) , Stéphane Vassilopoulos (2) , Matthieu Piel (6, 7) , Patricia Bassereau (3) , David Gonzalez-Rodriguez (12) , Cécile Leduc (13) , Emmanuel Lemichez (1)

1 Toxines bactériennes - Bacterial Toxins
2 Institut de Myologie
3 PCC - Laboratoire Physico-Chimie Curie [Institut Curie]
4 Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB
5 Epidémiologie et Analyse des Maladies Infectieuses - Infectious Disease Epidemiology and Analytics
6 Biologie Cellulaire et Cancer
7 Institut Pierre-Gilles de Gennes pour la Microfluidique
8 UTechS PBI - BioImagerie Photonique – Photonic BioImaging
9 IAH - Hub d'analyse d'images - Image Analysis Hub (Platform)
10 BRI - Benaroya Research Institute [Seattle]
11 CBMCT - UMR 3666 / U1143 - Chimie biologique des membranes et ciblage thérapeutique
12 LCP-A2MC - Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes
13 IJM (UMR_7592) - Institut Jacques Monod

The spontaneous opening of large transendothelial cell macroaperture (TEM) tunnels can accompany leukocyte diapedesis and is triggered by bacterial exoenzymes that inhibit RhoA-driven cytoskeleton contractility. Modelling the dynamics of TEM via a theoretical framework used for soft matter physics allowed us to depict the essential driving forces at play on the membrane to enlarge TEMs. In this study, we conducted multidisciplinary experiments to characterize the role respectively played by cavin-1-structured caveolae and non-caveolar caveolin-1 in plasma membrane mechanics and identify their functional effects on TEM size. The results pointed towards a contributing role for non-caveolar caveolin-1 in the membrane bending rigidity, a mechanical parameter we quantified in a model system of tubes pulled from plasma membrane spheres. Depletion of cavin-1-structured caveolae showed no effect on membrane rigidity, whereas caveolae controlled cell height favouring TEM nucleation. Hence, caveolae confer protection against exoenzyme EDIN-B in mice with staphylococcal septicaemia.

Domaines: Sciences du Vivant [q-bio]

Camille Morel, Eline Lemerle, Feng-Ching Tsai, Thomas Obadia, Nishit Srivastava, et al.. Caveolae govern plasma membrane mechanics to protect cells against EDIN B-induced transcellular tunnel formation and lethality from S. aureus septicaemia. 2022. ⟨hal-03795543⟩