Hybrid Lipids Increase the Probability of Fluctuating Nanodomains in Mixed Membranes

Abstract

A ternary mixture model is proposed to describe composition fluctuations in mixed membranes composed of saturated, unsaturated, and hybrid lipids (with one saturated and one unsaturated hydrocarbon chain). The hybrids are line-active and can reduce the packing incompatibility between the saturated and unsaturated lipids. We introduce a lattice model that extends previous studies by taking into account the dependence of the interactions of the hybrid lipids on their orientations in a simple way. A methodology to recast the free energy of the lattice model in terms of a continuous, isotropic field theory is proposed and used to analyze composition fluctuations in the one-phase region (above the critical temperature). The effect of hybrid lipids on fluctuation domains rich in saturated/unsaturated lipids is predicted. The correlation length of such fluctuations decreases significantly with increasing amounts of hybrids; this implies that nanoscale fluctuation domains are more probable compared to the case with no hybrids. Smaller correlated fluctuation domains arise even when the temperature is close to a critical point, where very large correlation lengths are normally expected. This decrease in the correlation length is largest as the hybrid composition tends toward a crossover value above which stripelike fluctuations are predicted. This crossover value defines the Lifshitz line. The characteristic wavelength of the stripelike fluctuations is large close to the Lifshitz point but decreases toward a molecular size in a membrane that contains only hybrids. Micrometer size, stripelike domains have recently been observed experimentally in giant unilamelar vesicles (GUVs) made of saturated, unsaturated, and hybrid lipids. These results suggest that the line activity of hybrid lipids in such mixtures may be significant only at large hybrid fractions; in that regime, the interface between domains can be diffuse and several hybrid molecules with correlated orientations can separate saturated and unsaturated lipid regions.

Seeing the Forest in Lieu of the Trees

“…However, the cell membrane contains only a small amount of lipids with two saturated tails. Later work suggests that the hybrid lipids serve both as the bulk and the line agents [29, 30]. In a recent paper [26], Schick shows that the interaction between membrane curvature and membrane composition can produce a modulated phase; a phase that exhibits periodic order in the composition over long length scales.…”

Size and mobility of lipid domains tuned by geometrical constraints

“…These raft-like domains grow several micrometers in size in giant unilamellar vesicles (GUVs) (7), while their mobility is preserved, whereas lipid domains in supported lipid bilayers are smaller but are largely immobile and do not form energy-minimized round shapes (10). Explanations for the size difference of lipid domains in native plasma membranes and model membranes range from the system's vicinity to a critical point (9), where density fluctuations prevail, over compositions with lipids having one saturated and one unsaturated fatty acid tail (11), coupling between composition and local membrane deformation (12)(13)(14), and the presence of the cortical cytoskeleton (15). It has been shown that attaching an artificial cytoskeleton made of actin or a tubulin homolog alters the shape and position of the ordered domains (16,17).…”

Atomic force microscopy of phase separation on ruptured, giant unilamellar vesicles

“…http://dx.doi.org/10.1101/250944 doi: bioRxiv preprint first posted online Jan. 20, 2018; enough to be relevant physiologically and if so, what forces stabilize the domains at the nanoscopic range. This motivates a broad range of experimental and theoretical studies of model lipid membrane systems [12][13][14][15] . Several potential factors have been proposed, including entropic force and mechanical repulsion caused by the difference of the intrinsic curvature of different phases 1,16,17 .…”