DHA-containing phospholipids control membrane fusion and transcellular tunnel dynamics

Meng-Chen Tsai (1, 2) , Lucile Fleuriot (1) , Sébastien Janel (3) , David Gonzalez-Rodriguez (4) , Camille Morel (2) , Amel Mettouchi (2) , Delphine Debayle (1) , Stéphane Dallongeville (5) , Jean-Christophe Olivo-Marin (5) , Bruno Antonny (1) , Frank Lafont (3) , Emmanuel Lemichez (2) , Hélène Barelli (1)

1 IPMC - Institut de pharmacologie moléculaire et cellulaire
2 Toxines bactériennes - Bacterial Toxins
3 CIIL - Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204
4 LCP-A2MC - Laboratoire de Chimie et Physique - Approche Multi-échelle des Milieux Complexes
5 BIA - Analyse d'images biologiques - Biological Image Analysis

Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (DHA-PLs) in physiology. Here, we investigated the impact of DHA-PLs on the dynamics of transendothelial cell macroapertures (TEMs) triggered by RhoA inhibition-associated cell spreading. Lipidomic analyses showed that human umbilical vein endothelial cells (HUVECs) subjected to a DHA diet undergo a 6-fold enrichment in DHA-PLs at the plasma membrane (PM) at the expense of monounsaturated oleic acid-containing PLs (OA-PLs). Consequently, DHA-PL enrichment at the PM induces a reduction in cell thickness and shifts cellular membranes towards a permissive mode of membrane fusion for transcellular tunnel initiation. We provide evidence that a global homeostatic control of membrane tension and cell cortex rigidity minimizes overall changes of TEM area through a decrease of TEM size and lifetime. Conversely, low DHA-PL levels at the PM lead to the opening of unstable and wider TEMs. Together, this provides evidence that variations of DHA-PL levels in membranes affect cell biomechanical properties.

Mots clés: Polyunsaturated phospholipids; Docosahexaenoic acid; DHA; Membrane fusion; Large-scale membrane dynamics; Endothelium; Transendothelial cell macroaperture; Bacterial toxin; Actin cytoskeleton

Domaines: Sciences du Vivant [q-bio]; Microbiologie et Parasitologie; Biologie cellulaire; Organisation et fonctions cellulaires [q-bio.SC]; Interactions cellulaires [q-bio.CB]

Meng-Chen Tsai, Lucile Fleuriot, Sébastien Janel, David Gonzalez-Rodriguez, Camille Morel, et al.. DHA-containing phospholipids control membrane fusion and transcellular tunnel dynamics. Journal of Cell Science, 2022, 135 (5), pp.jcs259119. ⟨10.1242/jcs.259119⟩. ⟨pasteur-03744949⟩