Phase diagrams and lipid domains in multicomponent lipid bilayer mixtures

Abstract

Understanding the phase behavior of biological membranes is helped by the study of more simple systems. Model membranes that have as few as 3 components exhibit complex phase behavior that can be well described, providing insight for biological membranes. A number of different studies are in agreement on general findings for some compositional phase diagrams, in particular, those that model the outer leaflet of animal cell plasma membranes. These model mixtures include cholesterol, together with one high-melting lipid and one low-melting lipid. An interesting finding is of two categories of such 3-component mixtures, leading to what we term Type I and Type II compositional phase diagrams. The latter have phase regions of macroscopic coexisting domains of {Lα+Lβ+Lo} and of {Lα+Lo}, with domains resolved under the light microscope. Type I mixtures have the same phase coexistence regions, but the domains seem to be nanoscopic. Type I mixtures are likely to be better models for biological membranes.

Order of lipid phases in model and plasma membranes

“…As the unseparated GPMVs also displayed a high GP m value at 20°C (Fig. S5A), the vesicles probably contain pre-existing nanoscopic domains in a microscopically uniform phase as previously suggested by Baumgart et al and others (25,42). Indeed, recent reports propose that GPMVs have a composition close to a critical point at which a decrease in temperature coalesces pre-existing nano-domains into a microscopic phase (43).…”

Molecular Convergence of Bacterial and Eukaryotic Surface Order

“…2). Membrane ordering both by sterol and by sterol-sphingolipid combination has been well documented (7)(8)(9)11); however, the disordering effect of peptide incorporation into such systems is beginning to emerge as a new theme. This work suggests that disorder may arise from disruption of lipid packing either by hydrophobic mismatch between protein transmembrane segments and the bilayer or by protruding side chains on the helix surface (16,17,48,49).…”

“…Regulation of lipid composition is one means to influence packing and thereby balance rigidity and fluidity (5,6). However, despite the increasing understanding of the physicochemical properties of model membranes (7)(8)(9), structural studies of cell membranes have begun to identify clear discrepancies between the model and the cell (10,11). Here integral membrane proteins account for one-third of the proteome (12), meaning that, unlike model systems, cell membranes, both eukaryotic and bacterial, are most appropriately understood as lipid-protein composites in which membrane protein occupies a substantial surface area (13,14).…”

Lipid Domain Co-localization Induced by Membrane Undulations

“…Multicomponent lipid bilayer membranes represent an interesting class of soft matter systems, displaying rich phase transition and associated compositional lipid domain formation behavior (1)(2)(3). In particular, ternary systems featuring coexisting compositional liquid-liquid phases (the so-called ''Lo'' phase, enriched in cholesterol and saturated lipids, and ''Ld'' phase, enriched in unsaturated lipids) are often employed as simple model systems of the plasma membrane of mammalian cells, where Lo-like lipid ''raft'' nanodomains (4,5) are believed to play a key role in several cellular processes, such as cell signaling and trafficking (6).…”