Cell membranes sustain phospholipid imbalance via cholesterol asymmetry.

Membranes are molecular interfaces that compartmentalize cells to control the flow of nutrients and information. These functions are facilitated by diverse collections of lipids, nearly all of which are distributed asymmetrically between the two bilayer leaflets. Most models of biomembrane structure and function often include the implicit assumption that these leaflets have similar abundances of phospholipids.

Caveolin assemblies displace one bilayer leaflet to organize and bend membranes.

Caveolin is a monotopic integral membrane protein, widely expressed in metazoa and responsible for constructing enigmatic membrane invaginations known as caveolae. Recently, the high-resolution structure of a purified human caveolin assembly, the CAV1-8S complex, revealed a unique organization of 11 protomers arranged in a tightly packed, radially symmetric spiral disc. One face and the outer rim of this disc are highly hydrophobic, suggesting that the complex incorporates into membranes by displacing hundreds of lipids from one leaflet.

Cryo-EM images of phase-separated lipid bilayer vesicles analyzed with a machine-learning approach.

Lateral lipid heterogeneity (i.e., raft formation) in biomembranes plays a functional role in living cells.

Seeing the Membrane from Both Sides Now: Lipid Asymmetry and Its Strange Consequences.

Almost all biomembranes are constructed as lipid bilayers and, in almost all of these, the two opposing monolayers (leaflets) have distinct lipid compositions. This lipid asymmetry arises through the concerted action of a suite of energy-dependent enzymes that maintain living bilayers in a far-from-equilibrium steady-state. Recent discoveries reveal that lipid compositional asymmetry imparts biophysical asymmetries and that this dualistic organization may have major consequences for cellular physiology.