The dependence of lipid asymmetry upon polar headgroup structure

Abstract

membrane surrounding the bacterial cytoplasm, it has been reported that phosphatidylinositol (PI) is preferentially located in the inner leafl et, phosphatidylglycerol (PG) is mainly located in the outer leafl et, and cardiolipin (CL) is distributed over both leafl ets in gram-positive bacteria Micrococcus lysodeikticus ( 5 ). Studies from Bacillus megaterium suggested PE mainly resides in the inner leafl et ( 6 ). In the outer membranes of gram-negative bacteria lipopolysaccharides are predominantly localized in the outer leafl et, while phospholipids are enriched in the inner leafl et ( 7-9 ). Several important functional roles of cellular membrane are closely associated with an asymmetrical lipid distribution. For example, dissipation of membrane lipid asymmetry, resulting in PS externalization on the outer leafl et of membrane, facilitates cell recognition and phagocytosis by macrophages during apoptosis ( 10-18 ). Exposure of PS on the outer cell surface has also been known to be involved in physiologically important phenomena including blood coagulation ( 19,20 ), cell adhesion ( 21-23 ), and myotube formation ( 24 ).To emulate cell membranes more closely, a number of methods have been developed to try to obtain asymmetric lipid bilayers (model membranes) ( 25-45 ). However, methods to form asymmetric lipid vesicles with a wide variety of lipid compositions and highly controlled lipid distribution in each leafl et have been lacking. To tackle this problem, our laboratory has developed methods to prepare asymmetric vesicles using methyl-␤ -cyclodextrin The inner and outer leafl et of many cellular membranes exhibits a difference in lipid composition. This difference is called lipid asymmetry. For example, in eukaryotic cells, the choline-containing lipids sphingomyelin (SM) and phosphatidylcholine (PC) are predominantly located in the outer leafl et of the plasma membrane, while the aminecontaining phospholipids phosphatidylethanolamine (PE) and phosphatidylserine (PS) are largely or fully confi ned to the plasma membrane inner leafl et ( 1-4 ). Membrane asymmetry is also observed in prokaryotic cells. Although it is diffi cult to determine lipid distribution in the leafl ets of the

Lateral organization, bilayer asymmetry, and inter-leaflet coupling of biological membranes

“…These two populations are mixed and incubated with cyclodextrin. The choice of cyclodextrin depends on the presence or lack of cholesterol, with methyl-β-cyclodextrin useful for pure lipid systems 29,30,63,80 and hydroxypropyl-α-cyclodextrin used when cholesterol is present in the acceptor ULVs [80][81][82][83] . This approach has proven to be flexible, producing model systems that closely mimic the mammalian plasma membranes (SM and/or PC outside and PE/PS inside), and in which cholesterol content can be readily varied between 0 and 50 mol%.…”

Lipid Structure and Composition Control Consequences of Interleaflet Coupling in Asymmetric Vesicles

“…Net flow of cholesterol between leaflets also may have a significant influence on coupling. Although cyclodextrin-catalyzed lipid exchange seems to maintain lipid balance between leaflets (18,19,27,51), a small net deficit or surplus of outer-leaflet lipid could result from exchange. This could be balanced out by a movement of cholesterol toward the leaflet with a lipid deficit and/or an imbalance between inner-and outer-leaflet lipid that could affect lipid packing in the more crowded and less crowded leaflets, especially when cholesterol is not present.…”

Vesicles in Nature and the Laboratory: Elucidation of Their Biological Properties and Synthesis of Increasingly Complex Synthetic Vesicles

“…The current lifetime is in the order of hours to days and is strongly dependent on the lipid structure. [91] Thus,strategies to prepare more stable artificial asymmetric vesicles are desirable.…”