Biophys. J. 103, 2311–2319 (2012)

Credit: SALVATORE CHIANTIA

The inner and outer leaflets of the plasma membrane maintain a compositional asymmetry, with sphingomyelin (SM) found mostly on the outer leaflet and lipids such as phosphatidylserine and phosphatidylethanolamine found mostly in the inner leaflet. Another difference between leaflets is in the propensity to form lipid rafts: inner-leaflet lipids form homogenous membranes that do not form rafts, but the outer-leaflet lipids can form rafts by themselves. However, the leaflets are coupled in some fashion, as outer-leaflet lipids can influence organization of inner-leaflet signaling proteins. To gain insight into the mechanisms of interleaflet coupling, Chiantia and London used fluorescence correlation spectroscopy to monitor the diffusion of lipids of various acyl chain length and saturation within the two leaflets of asymmetric giant unilamellar vesicles. They found that outer-leaflet SM enriched with acyl chains longer than the sphingoid base, which allows them to reach the opposing monolayer, slows the inner-leaflet lipids and increases coupling. The authors also observed that with a shorter acyl chain, SM could slow lipid dynamics in asymmetric membranes, with inner-leaflet lipids having one saturated and one unsaturated acyl chain. Although there was high coupling between the leaflets in terms of lipid diffusion, there was no coupling of structural order (that is, of raft-like domain formation) between the two leaflets. These results suggest that acyl chain interdigitation modulates coupling between leaflets of signaling membranes.