Chain ordering of hybrid lipids can stabilize domains in saturated/hybrid/cholesterol lipid membranes

We use a liquid-crystal model to predict that hybrid lipids (lipids that have one saturated and one unsaturated tail) can stabilize line interfaces between domains in mixed membranes of saturated lipids, hybrid lipids, and cholesterol (SHC membranes). The model predicts the phase separation of SHC membranes with both parabolic and loop binodals depending on the cholesterol concentration, modeled via an effective pressure. In some cases, the hybrid lipids can reduce the line tension to zero in SHC membranes at temperatures that approach the critical temperature as the pressure is increased. The differences in the hybrid saturated tail conformational order in bulk and at the interface are responsible for the reduction of the line tension. Copyright c © EPLA, 2010 Introduction. – The lipid raft hypothesis suggests that nanoscopic domains in biological membranes play an important role in a range of cellular functions [1,2]. Fluorescence microscopy studies show that membranes, comprised of saturated lipids with two saturated tails, unsaturated lipids with two (partially) unsaturated tails, and cholesterol (SUC membranes) exhibit phase separation into domains of liquid-disordered phase (Ld phase) that coexist with domains of liquid-ordered phase (Lo phase) [3]. The Ld phase is rich in unsaturated lipids and the tails of the lipids are disordered, while the Lo phase is rich in saturated lipids and cholesterol and the tails of the lipids are more ordered [4]. The lipid raft hypothesis in biological membranes envisages domains on the order of 10–100 nm that are stable or metastable [2]. However, as is usually the case in macroscopic phase separation, domains in model SUC membranes exhibit coarsening due to the positive line tension and their size eventually reaches the order of the system size, i.e. 1–10μm [3]. One reason for the discrepancy in the domain size between model SUC and biological membranes may be that lipids with two unsaturated tails are only minor components of biological membranes and not commonly found. On the other hands, lipids with one saturated (a)E-mail: [email protected] and one unsaturated tail, e.g. POPC or SOPC, here termed “hybrid” lipids are major components of biological membranes [5,6]. High-resolution techniques, e.g. fluorescence resonance energy transfer [7,8] and antibody reporters [9], suggest that membranes containing saturated lipids, hybrid lipids, and cholesterol (SHC membranes) show nanoscopic domains in some regions of their phase diagrams. However, this is somewhat controversial, since coarsening domains were also observed in SHC membranes by fluorescence microscopy [10]. It is possible that nanoscopic domains are only stable in a limited part of the phase diagram and/or nanoscopic domains are only metastable. This motivated us to theoretically study the phase separation and the line tension between domains in SHC membranes. The chain packing theory [11,12] suggests that the chain packing incompatibility between the tails of saturated lipids and the permanently kinked tails of unsaturated lipids drives the phase separation in SUCmembranes when the tails of saturated lipids are relatively ordered. This implies that chain packing incompatibility at the interface gives rise to the positive line tension between domains in this membrane. A positive line tension drives domain coarsening, thus, finite-size domains can only be stable if the line tension is reduced to zero; the finite size is then determined by packing considerations at the interface [13].