The lipid network

Abstract

Natural cell membranes are composed of a remarkable variety of lipids, which provide specific biophysical properties to support membrane protein function. An improved understanding of this complexity of membrane composition may also allow the design of membrane active drugs. Crafting a relevant model of a cell membrane with controlled composition is becoming an art, with the ability to reveal the molecular mechanisms of biological processes and lead to better treatment of pathologies. By matching physiological observations from in vivo experiments to high-resolution information, more easily obtained from in vitro studies, complex interactions at the lipid interface are determined. The role of the lipid network in biological membranes is, therefore, the subject of increasing attention.

Keywords: Lipid composition; Lipid targeting; Lipid transformation; Membrane active peptides; Model membrane.

Fig. 1

Timeline of various lipid discoveries. POPC 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine. PG glycero-3-phosphoglycerol. DPPG 1,2 -dipalmitoyl-sn-glycero-3-phosphoglycerol. GM1 monosialotetrahexosylganglioside. PA glycero-3-phosphatidic acid. PE glycero-3-phosphoethanolamine. PS glycero-3-phosphoserine. PI glycero-3-phosphoinositol

Fig. 2

Timeline of membrane structure conception. (1) Danielli and Dawson’s model of the protein layer (red) coating the lipid bilayer (blue). (2) In the gel L_β phase , acyl chains are rigid; increasing the temperature promotes transition to the liquid-crystalline L_α phase where acyl chains are highly disordered. (3) Singer and Nicolson’s fluid mosaic model: the membrane model is described to be fluid because of lipids (blue/grey) and proteins (red) diffuse laterally, meaning the membrane is not solid. The membrane is depicted as mosaic because it is composed of many macromolecules having different properties, such as glycolipids (black) or cholesterol (yellow). (4) The lipid whisker model represents the latest evolution in membrane structure and function understanding. When lipids acyl chains are oxidized (green), they become hydrophilic and are exposed towards the aqueous phase, serving as signal receptor for molecules such as enzymes (béchamel)