Hybrid and Nonhybrid Lipids Exert Common Effects on Membrane Raft Size and Morphology

Abstract

Nanometer-scale domains in cholesterol-rich model membranes emulate lipid rafts in cell plasma membranes (PMs). The physicochemical mechanisms that maintain a finite, small domain size are, however, not well understood. A special role has been postulated for chain-asymmetric or hybrid lipids having a saturated sn-1 chain and an unsaturated sn-2 chain. Hybrid lipids generate nanodomains in some model membranes and are also abundant in the PM. It was proposed that they align in a preferred orientation at the boundary of ordered and disordered phases, lowering the interfacial energy and thus reducing domain size. We used small-angle neutron scattering and fluorescence techniques to detect nanoscopic and modulated liquid phase domains in a mixture composed entirely of nonhybrid lipids and cholesterol. Our results are indistinguishable from those obtained previously for mixtures containing hybrid lipids, conclusively showing that hybrid lipids are not required for the formation of nanoscopic liquid domains and strongly implying a common mechanism for the overall control of raft size and morphology. We discuss implications of these findings for theoretical descriptions of nanodomains.

Docosahexaenoic acid promotes micron scale liquid-ordered domains. A comparison study of docosahexaenoic versus oleic acid containing phosphatidylcholine in raft-like mixtures

“…An explanation for this observation is that POPC and PDPC exhibit specific partition into the L o domains, particularly at low temperatures (4°C), the POPC seems to have more pronounced ability to partition into L o compared to PDPC. Our results are in accordance with data coming from molecular simulations using hybrid lipids showing that POPC is able to partition into L o domains, where such lipids decrease the order and compactness of the phase [72,73]. The authors also stated that the degree of unsaturation of the sn-2 fatty acid chains characterizes the lineactant properties of the lipid with POPC being a weak lineactant compared to more unsaturated fatty acid lipids.…”

Physical mechanisms of micro- and nanodomain formation in multicomponent lipid membranes

“…Intriguingly, experimental studies of a four-component mixture consisting of purely nonhybrid lipids revealed a scenario which is very similar to that shown in Fig. 2 [133]. In that work, DOPC was not substituted with the hybrid lipid POPC, but with the fully saturated lipid DLPC.…”

The mystery of membrane organization: composition, regulation and roles of lipid rafts

“…Raman spectroscopy is another label-free technique that has been successfully applied to monitor membrane domain composition 73 . Likewise, small-angle neutron scattering has also been used to detect raft-like domains 74 and their size 75 . Finally, electron microscopy has the necessary resolution for obtaining a snapshot of molecular arrangements at the cell surface, and a number of studies of outer and inner leaflet lipid tethered proteins, including GPI-anchored proteins, glycolipids and Ras proteins, have revealed the nanoscopic organization of proteins in rafts 76 .…”