Lipid phases phase coexistence

As discussed above, lipid membranes are dynamic structures with heterogeneous structure involving different lipid domains. The coexistence of different kinds of domains implies that boundaries must exist. The appearance of leaky interfacial regions, or defects, has been suggested to play a role in abrupt changes in solute permeabilities in the two-phase coexistence regions [91,92]. 

Phase behavior of lipid mixtures is a much more difficult problem, due to nonideal mixing of lipid components. Ideal mixing implies like and unlike lipids have the same intermolecular interactions, while nonideal mixing results from differential interactions between lipid types. If the difference is too great, the two components will phase separate. While phase separation and lateral domain formation have been observed in many experiments, we lack a molecular-level physical description of the interactions between specific lipids that cause the macroscopic behavior. The chemical potential of a lipid determines phase separation, as phase coexistence implies the chemical potential of each type of lipid is equal in all phases of the system [3,4],... 

A more interesting problem from both the experimental and theoretical point of view is the lateral diffusion of phospholipids in mixtures of lipids, when both solid and fluid phases coexist. At least three questions arise in connection with this problem. (1) What is the rate of lateral diffusion of phospholipids in solid solution domains (2) To what extent do solid solution domains act as obstacles to the lateral diffusion of lipid molecules in fluid domains (3) To what extent are there composition and density fluctuations present in fluid lipid bilayers, and to what extent do these fluctuations affect lateral diffusion Let us consider these questions one at a time, bearing in mind that these questions may to some extent be interrelated. 

As mentioned in my report, in addition to large coexisting domains of solid and fluid phase lipids, there may be fluctuations of composition and density in the fluid-lipid phase that are not seen in the electron microscope but that may affect nuclear magnetic resonance spectra. 

A partially fluorinated lipid (LL-8-8) was found to form stripe-like microdomains at the gas-liquid phase coexistence region, when spread on water as a Langmuir monolayer [28]. 

Quantitative investigation of recognition of this pair of liposomes was performed with isothermal titration microcalorimetry (ITC). It has been found that one-to-one binding between adenine and barbituric acid in the lipid/water/lipid interface occurs. However at T= 58°C, above the main lipid phase transition, the situation is different and no liposomal binding is detected. This is mainly due to the molecular disorder within the bilayer (liquid-disordered/liquid ordered phase coexistence) that limits the capacity of complementary moieties to bind, due to the weakening of the hydrogen bonds at these high temperatures. 

Phase coexistence in lipid bilayers may be an important physical property for membranes of cells. When two phases coexist in a bilayer, depending upon the relative mass fractions of the phases and the shapes of their domains, one of the phases is percolative (physically continuous) and the other is nonpercola-tive (physically discontinuous or dispersed as isolated domains). Changes in the physico-chemical properties of the membrane (lateral pressure, temperature, and chemical composition are the most relevant for biological membranes) result in interconversion between the two phases—one phase grows at the expense of the other. In phase-separated systems of this type, a critical mass ratio of phases called the percolation threshold, at which the previously continuous phase becomes discontinuous and the previously discontinuous phase becomes continuous, becomes... 

NMR Overview of Application in Chemical Biology PHYSICAL PROPERTIES PHASE COEXISTENCE IN LIPID BILAYERS... 

Substantial literature has been published on studies of lipid domains in supported bilayers. Many have investigated lipid mixtures with coexisting gel and liquid-crystalline phases by atomic force (AFM), epifiuorescence, and near-field fluorescence microscopy (NSOM) (see, for example. References (44 7)). 

When a bicontinuous cubic lipid-water phase is mechanically fragmented in the presence of a liposomal dispersion or of certain micellar solutions e.g. bile salt solution), a dispersion can be formed with high kinetic stability. In the polarising microscope it is sometimes possible to see an outer birefringent layer with radial symmetry (showing an extinction cross like that exhibited by a liposome). However, the core of these structures is isotropic. Such dispersions are formed in ternary systems, in a region where the cubic phase coexists in equilibrium with water and the L(x phase. The dispersion is due to a localisation of the La phase outside cubic particles. The structure has been confirmed by electron microscopy by Landh and Buchheim [15], and is shown in Fig. 5.4. It is natural to term these novel structures "cubosomes". They are an example of supra self-assembly. 

Figure 1 represents the isotherms for two lipid components which are miscible in the condensed monolayer state. The major feature of the isotherms for the pure components (1 0, 0 1) is the transition region in which the surface pressure is independent of surface area here the limits of the transition region are at the low area end, Ac, and at the high area end, Ax. These areas are characteristic of each lipid and represent the area per molecule of the lipid in the condensed and vapor states (10). For an equimolar mixture of the two components (1 1), the surface pressure in the transition region depends on the surface area according to the phase rule (11, 12, 13, 14), two surface phases coexist here a condensed phase of lipids and the surface vapor phase. To obtain the activity coefficient of the ith component in the condensed phase the following relation may be used ... 

In order to observe the concentration fluctuations caused by the gel-fluid phase coexistence in the above-mentioned binary phospholipid mixtures, SANS studies in combination with the H/D substitution technique were performed. Under these so-called matching conditions, no SANS signal is obtained for homogeneously mixed lipids in the all-gel or all-fluid phases, since then the scattering length density is constant over the whole sample. However, in the case of gel-fluid phase heterogeneities, SANS occurs due to the different compositions and... 

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