Liquid disorder

Recently, due to increased interest in membrane raft domains, extensive attention has been paid to the cholesterol-dependent liquid-ordered phase in the membrane (Subczynski and Kusumi 2003). The pulse EPR spin-labeling DOT method detected two coexisting phases in the DMPC/cholesterol membranes the liquid-ordered and the liquid-disordered domains above the phase-transition temperature (Subczynski et al. 2007b). However, using the same method for DMPC/lutein (zeaxanthin) membranes, only the liquid-ordered-like phase was detected above the phase-transition temperature (Widomska, Wisniewska, and Subczynski, unpublished data). No significant differences were found in the effects of lutein and zeaxanthin on the lateral organization of lipid bilayer membranes. We can conclude that lutein and zeaxanthin—macular xanthophylls that parallel cholesterol in its function as a regulator of both membrane fluidity and hydrophobicity—cannot parallel the ability of cholesterol to induce liquid-ordered-disordered phase separation. 

In aqueous systems, membrane lipids may exist in a gel-like solid state or as a two-dimensional liquid. In the case of pure phospholipids, these states interconvert at a well-defined transition temperature, Tc, that increases with alkyl chain length and decreases with introduction of alkyl chain unsaturation. In cell membranes, which have marked heterogeneity in both the polar and nonpolar domains of the bilayer, this state is described as liquid disordered . The presence of sufficient sphingolipids, with... 

There is a large cholesterol concentration gradient in cells from 0-5 mol% in the ER membrane to 25-40 mol% in the plasma membrane [12], Cholesterol has a condensing effect on liquid-crystalline bilayers, causing increased rigidity and thickness [13]. At high concentrations, cholesterol induces an intermediate liquid-ordered phase between the gel and liquid-disordered phases [13]. A number of... 

Although the lipid bilayer structure is quite stable, its individual phospholipid and sterol molecules have some freedom of motion (Fig. 11-15). The structure and flexibility of the lipid bilayer depend on temperature and on the kinds of lipids present. At relatively low temperatures, the lipids in a bilayer form a semisolid gel phase, in which all types of motion of individual lipid molecules are strongly constrained the bilayer is paracrystalline (Fig. ll-15a). At relatively high temperatures, individual hydrocarbon chains of fatty acids are in constant motion produced by rotation about the carbon-carbon bonds of the long acyl side chains. In this liquid-disordered state, or fluid state (Fig. 11—15b), the interior of the bilayer is more fluid than solid and the bilayer is like a sea of constantly moving lipid. At intermediate temperatures, the lipids exist in a liquid-ordered state there is less thermal motion in the acyl chains of the lipid bilayer, but lateral movement in the plane of the bilayer still takes place. These differences in bilayer state are easily observed in liposomes composed of a single lipid,... 

Lipids in a biological membrane can exist in liquid-ordered or liquid-disordered states in the latter state, thermal motion of acyl chains makes the interior of the bilayer fluid. Fluidity is affected by temperature, fatty acid composition, and sterol content. 

In the 1970s, the fluid mosaic concept emerged as the most plausible model to account for the known structure and properties of biological membranes [41]. The fact that membranes exist as two-dimensional fluids (liquid disordered) rather than in a gel state (solid ordered) was clearly demonstrated by Frye and Ededin [42], who showed that the lipid and protein components of two separate membranes diffuse into each other when two different cells were fused. Since that time, numerous studies have measured the diffusion coefficient of lipids and proteins in membranes, and the diffusion rates were found to correspond to those expected of a fluid with the viscosity of olive oil rather than a gel phase resembling wax. 

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. 

Liquids, Gases and Disordered Solids. Liquids, disordered solids, gases, and single crystals can diffract X rays. For liquids and disordered solids, where there is no long-range order, and the short-range order extends from 0 to maybe 1 or 2 nm, the diffraction consists of very broad maxima in the intensity function 7(s), where s is the scattering vector defined in Eq. (11.23.2). The one-dimensional Fourier transform of I(s) is the radial distribution function R(r) ... 

Marsh (38) has listed several measured values of the elastic moduli of lipid bilayers. Typically, the area compressibility moduli are in the range of 200-250 mNm for fully hydrated symmetric bilayers in the L phase prepared from phosphatidylcholines, and they are not very dependent on the degree of saturation of the acyl chains. Cholesterol has a significant effect on the area compressibility modulus of a bilayer. Thus, AT A for bilayers of l-stearoyl-2-oleoylphosphatidylcholine (SOPC) increases from 235 mN m in the absence of cholesterol (La liquid-disordered phase) to 640 mN m in bilayers... 

The lipids in a lipid bilayer may translocate across the bilayer from one monolayer to the apposed monolayer. This transmembrane translocation process, which is also known as flip-flop, is slow for lipids with large polar head groups such as glyc-erolipids and sphingophospholipids but can be fast in the case of lipids with very small polar moieties such as cholesterol. Typical first-order rate constants for transmembrane translocation of a phospholipid-like molecule in liquid-disordered phase bilayers prepared from l-palmitoyl-2-oleoylphosphatidylcholine (POPC) are s and may be about 10-fold slower in... 

Moreno MJ, Estronca LMB, Vaz WLC. Translocation of phospholipids and dithionite permeability in liquid-ordered and liquid-disordered membranes. Biophys. J. 2006 91 873-881. 

A few proteins exist that sequester PIP2 in a cholesterol-dependent manner. One of these proteins is the N-terminal myristoylated peptide of NAP-22 (33, 34). Combined confocal microscopy and AFM show that this peptide forms new cholesterol-rich domains within the liquid-disordered domain to which it attracts PIP2 (31). In addition, a peptide segment of caveolin promotes the formation of membrane domains containing both cholesterol and PIP2 (35). 

Although some membrane proteins are known to interact with cholesterol, cholesterol interactions with other lipids have been studied much more thoroughly. Most notably, cholesterol interacts strongly with sphingomyelin, perhaps by forming complexes, which results in a liquid-liquid phase separation of cholesterol-rich and cholesterol-poor phases (13). The cholesterol-rich phases exhibit more chain order and therefore are referred to as liquid-ordered (lo) phases, whereas the cholesterol-poor phases are called liquid-disordered (Id) phases. 

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