DHA-phospholipids control membrane fusion and transcellular tunnel dynamics

Authors:

Tsai, M. C., Fleuriot, L., Janel, S., Gonzalez-Rodriguez, D., Morel, C., Mettouchi, A., ... & Barelli, H.

Keywords:

Polyunsaturated phospholipids, Docosahexaenoic acid (DHA), Membrane fusion, Large scale membrane dynamics, Endothelium, Transendothelial cell macroaperture, Bacterial toxins, Actin cytoskeleton

Abstract:

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.

< Back to publications

Full article >