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Journal of Cell Science
DHA-phospholipids control membrane fusion and transcellular tunnel dynamics
Tsai, M. C., Fleuriot, L., Janel, S., Gonzalez-Rodriguez, D., Morel, C., Mettouchi, A., ... & Barelli, H.
Polyunsaturated phospholipids, Docosahexaenoic acid (DHA), Membrane fusion, Large scale membrane dynamics, Endothelium, Transendothelial cell macroaperture, Bacterial toxins, Actin cytoskeleton
Metabolic studies and animal knockout models point to the critical role of polyunsaturated docosahexaenoic acid (22:6, DHA)-containing phospholipids (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 show that human umbilical vein endothelial cells (HUVECs) subjected to DHA-diet undergo a 6-fold enrichment in DHA-PLs at plasma membrane (PM) at the expense of monounsaturated OA-PLs. Consequently, DHA-PLs enrichment at the PM induces a reduction of 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 leads to the opening of unstable and wider TEMs. Together, this provides evidence that variations of DHA-PLs levels in membranes affect cell biomechanical properties.