Lipid-lipid interactions across a phospholipid bilayer were probed by measuring the nearest-neighbor preferences of exchangeable phospholipid monomers derived from 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine (DMPE) and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE) in the presence of nonexchangeable DMPE- or DSPE-based dimers. Each of these permanent dimers promoted homophospholipid association to the same extent, whereas the corresponding nonexchangeable monomers were without effect. These results support a model in which the longer phospholipids in one monolayer leaflet preferentially associate with shorter ones in the adjoining monolayer. Such transbilayer complementarity is likely to play an important role in stabilizing biological membranes and also in promoting a compositional interdependence of their two lipid leaflets.

A series of molecular umbrella conjugates, derived from cholic acid, deoxycholic acid, spermidine, lysine, and 5-mercapto-2-nitrobenzoic acid, have been synthesized and found capable of transporting an attached 16-mer oligonucleotide (S-dT16) across liposomal membranes made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyldglycerol (POPG), and cholesterol [POPC/POPG/cholesterol (65/5/30; mol/mol/mol, v/v/v)] at 37 degrees C. Those molecular umbrellas containing four choloyl (or deoxycholoyl) groups resulted in significantly faster rates of transport as compared to those containing only two such moieties. A model that accounts for these membrane transport processes is proposed.

The mixing properties of exchangeable phospholipids, derived from 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine, with an exchangeable form of cholesterol have been used to monitor the transition from the liquid-disordered to the liquid-ordered phase in cholesterol-containing bilayers, made from 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-distearoyl-sn-glycero-3-phosphocholine, respectively.

The mixing behavior of exchangeable, disulfide-based mimics of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and cholesterol has been examined as a function of temperature in host membranes made from DPPC and cholesterol in the liquid-disordered phase (ld), in the liquid-ordered phase (lo), and in the liquid-disordered/liquid-ordered coexistence region (ld/lo). In the ld region, lipid mixing was found to be temperature insensitive, reflecting close to ideal behavior. In contrast, a significant temperature dependence was observed in the lo phase from 45 to 60 degrees C, when 35 or 40 mol % sterol was present. In this region, sterol-phospholipid association was characterized by DeltaHo = -2.06 +/- 0.14 kcal/mol of phospholipid and DeltaS degrees = -4.48 +/- 0.44 cal/K mol of phospholipid. From 60 to 65 degrees C, the mixing of these lipids was found to be insensitive to temperature, and sterol-phospholipid association was now entropy driven; that is, DeltaHo = -0.23 +/- 0.38 kcal/mol of phospholipid and DeltaS degrees = +1.68 +/- 1.12 cal/K mol of phospholipid. In the liquid-disordered/liquid-ordered coexistence region, changes in lipid mixing reflect changes in the phase composition of the membrane.

One of the most challenging questions that relates to the structure and function of biological membranes is whether the two halves of the bilayer "talk" to each other. In this paper, we show how the pertubation of the lateral organization of one leaflet of a fluid phospholipid bilayer by an external agent also alters the lateral organization of the adjoining leaflet. In addition, we show that the energy involved in such cross-talk corresponds to ca. 100 cal/mol of phospholipid. These findings provide a basis for expecting similar cross-talk to exist in cell membranes.