What’s the Buzz? – Membrane Leaflet Crosstalk


The cover image for the January 9 issue of Biophysical Journal is an artistic rendering of vesicles made up of lipids with shapes resembling either an inverted cone (cyan heads), or a right cylinder (yellow heads). In one type of vesicle, the cyan and yellow lipids populate the inner and outer leaflets, respectively, while in the other type of vesicle, they are reversed. A closer look reveals that the vesicle with an inner leaflet of cyan lipids has acyl chains that are “straight” in both leaflets, implying an ordered state or gel phase. However, when the yellow lipids are placed in the inner leaflet, their acyl chains go from being straight to being “wavy,” implying hydrocarbons in a disordered state or fluid phase. The difference between the two types of vesicles is related to interleaflet coupling. In other words, when the inverted cone (cyan) lipids are located in the inner leaflet, they are able to “communicate” information about their ordered state to the right cylinder with yellow lipids in the outer leaflet. Interestingly, when their places are inverted, this communication is lost.

We studied ~100 nm diameter asymmetric lipid vesicles composed of palmitoyl oleoyl phosphatidylethanolamine (POPE) and palmitoyl oleoyl phosphatidylcholine (POPC). Cyan lipids in the cover image represent POPE and yellow lipids represent POPC. Combining elastic X-ray/neutron scattering techniques with differential scanning calorimetry, dynamic light scattering, nuclear magnetic resonance spectroscopy, and cryo-electron microscopy allowed us to compare leaflet- specific structural properties of vesicles with POPE-rich inner leaflets and POPC-rich outer leaflets, to vesicles with reversed lipid asymmetry. Our data reveal when the inner leaflet is predominantly made up of POPE, it is able to induce a gel phase in the POPC-enriched outer leaflet. When reversed, this communication between the leaflets is lost and the POPC-enriched inner leaflet remains fluid. This can be understood in terms of an energetic benefit of locating inverted cone-shaped lipids, such as POPE, in the inner monolayer, which is better able to match the overall vesicle curvature, compared to when it is located in the outer lipid monolayer.

Signal transduction and intercellular communication are essential for membranes, and are mostly due to integral proteins. However, physiological processes that require communication between, for example, receptors secreted to the exoplasm and components of signal transduction pathways in the cytoplasm, may rely on a bilayer leaflet coupling mechanism such as the one described  in our manuscript.

-Barbara Eicher, Drew Marquardt, Frederick Heberle, Ilse Letofsky-Papst, Gerald N. Rechberger, Marie-Sousai Appavou, John Katsaras, Georg Pabst


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