Tore Skotland1,2, Alicia Llorente1,2,3 and Kirsten Sandvig1,2,4 1Department of Molecular Cell Biology, Institute for Cancer Research, Oslo University Hospital-The Norwegian Radium Hospital, 0379 Oslo, Norway 2Centre for Cancer Cell Reprogramming, Faculty of Medicine, University of Oslo, 0379 Oslo, Norway 3Department of Mechanical, Electronics and Chemical Engineering, Oslo Metropolitan University, 0167 Oslo, Norway 4Department of Molecular Biosciences, University of Oslo, 0316 Oslo, Norway Correspondence: toreskouio.no

Extracellular vesicles, such as exosomes, can be used as interesting models to study the structure and function of biological membranes as these vesicles contain only one membrane (i.e., one lipid bilayer). In addition to lipids, they contain proteins, nucleic acids, and various other molecules. The lipid composition of exosomes is here compared to HIV particles and detergent-resistant membranes, which also have a high content of sphingolipids, cholesterol, and phosphatidylserine (PS). We discuss interactions between the lipids in the two bilayers, and especially those between PS 18:0/18:1 in the inner leaflet and the very-long-chain sphingolipids in the outer leaflet, and the importance of cholesterol for these interactions. We also briefly discuss the involvement of ether-linked phospholipids (PLs) in such lipid raft-like structures, and the possible involvement of these and other lipid classes in the formation of exosomes. The urgent need to improve the quality of quantitative lipidomic studies is highlighted.