Membrane lipid bilayers fluidity

Cholesterol - an essential component of mammalian cells - is important for the fluidity of membranes. With a single hydroxy group, cholesterol is only weakly am-phipathic. This can lead to its specific orientation within the phospholipid structure. Its influence on membrane fluidity has been studied most extensively in erythrocytes. It was found that increasing the cholesterol content restricts molecular motion in the hydrophobic portion of the membrane lipid bilayer. As the cholesterol content of membranes changes with age, this may affect drug transport and hence drug treatment. In lipid bilayers, there is an upper limit to the amount of cholesterol that can be taken up. The solubility limit has been determined by X-ray diffraction and is... 

The use of Upid bilayers as a relevant model of biological membranes has provided important information on the structure and function of cell membranes. To utilize the function of cell membrane components for practical applications, a stabilization of Upid bilayers is imperative, because free-standing bilayer lipid membranes (BLMs) typically survive for minutes to hours and are very sensitive to vibration and mechanical shocks [156,157]. The following concept introduces S-layer proteins as supporting structures for BLMs (Fig. 15c) with largely retained physical features (e.g., thickness of the bilayer, fluidity). Electrophysical and spectroscopical studies have been performed to assess the appUcation potential of S-layer-supported lipid membranes. The S-layer protein used in aU studies on planar BLMs was isolated fromB. coagulans E38/vl. 

The lipid molecule is the main constituent of biological cell membranes. In aqueous solutions amphiphilic lipid molecules form self-assembled structures such as bilayer vesicles, inverse hexagonal and multi-lamellar patterns, and so on. Among these lipid assemblies, construction of the lipid bilayer on a solid substrate has long attracted much attention due to the many possibilities it presents for scientific and practical applications [4]. Use of an artificial lipid bilayer often gives insight into important aspects ofbiological cell membranes [5-7]. The wealth of functionality of this artificial structure is the result of its own chemical and physical properties, for example, two-dimensional fluidity, bio-compatibility, elasticity, and rich chemical composition. 

Major determinants of membrane fluidity may be grouped within two categories [53] (1) intrinsic determinants, i.e., those quantifying the membrane composition and phase behavior, and (2) extrinsic determinants, i.e., environmental factors (Table 1). In general, any manipulation that induces an increase in the molal volume of the lipids, e.g., increase in temperature or increase in the fraction of unsaturated acyl chains, will lead to an increase in membrane fluidity. In addition, several intrinsic and extrinsic factors presented in Table 1 determine the temperature at which the lipid molecules undergo a transition from the gel state to liquid crystalline state, a transition associated with a large increase in bilayer fluidity. 

Before the first indication of the existence of cannabinoid receptors, the prevailing theory on the mechanism of cannabinoid activity was that cannabinoids exert their effects by nonspecific interactions with cell membrane lipids (Makriyannis, 1990). Such interactions can increase the membrane fluidity, perturb the lipid bilayer and concomitantly alter the function of membrane-associated proteins (Loh, 1980). A plethora of experimental evidence suggests that cannabinoids interact with membrane lipids and modify the properties of membranes. However, the relevance of these phenomena to biological activities is still only, at best, correlative. An important conundrum associated with the membrane theories of cannabinoid activity is uncertainty over whether cannabinoids can achieve in vivo membrane concentrations comparable to the relatively high concentrations used in in vitro biophysical studies (Makriyannis, 1995). It may be possible that local high concentrations are attainable under certain physiological circumstances, and, if so, some of the cannabinoid activities may indeed be mediated through membrane perturbation. 

The binding of carotenoids within the lipid membranes has two important aspects the incorporation rate into the lipid phase and the carotenoid-lipid miscibility or rather pigment solubility in the lipid matrix. The actual incorporation rates of carotenoids into model lipid membranes depend on several factors, such as, the kind of lipid used to form the membranes, the identity of the carotenoid to be incorporated, initial carotenoid concentration, temperature of the experiment, and to a lesser extent, the technique applied to form model lipid membranes (planar lipid bilayers, liposomes obtained by vortexing, sonication, or extrusion, etc.). For example, the presence of 5 mol% of carotenoid with respect to DPPC, during the formation of multilamellar liposomes, resulted in incorporation of only 72% of the pigment, in the case of zeaxanthin, and 52% in the case of (1-carotene (Socaciu et al., 2000). A decrease in the fluidity of the liposome membranes, by addition of other... 

We would like to point out that an order parameter indicates the static property of the lipid bilayer, whereas the rotational motion, the oxygen transport parameter (Section 4.1), and the chain bending (Section 4.4) characterize membrane dynamics (membrane fluidity) that report on rotational diffusion of alkyl chains, translational diffusion of oxygen molecules, and frequency of alkyl chain bending, respectively. The EPR spin-labeling approach also makes it possible to monitor another bulk property of lipid bilayer membranes, namely local membrane hydrophobicity. 

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. 

The membrane is a dynamic assembly and things are diffusing rapidly in the plane of the bilayer. The middle of the bilayer has been likened to olive oil. As with oil, cooling the lipid bilayer will cause the hydrocarbons to become more ordered (structured). The side chains pack closer to each other, and the fluidity of the membrane is lower. Things that disrupt the ability of the side chains to pack in a regular fashion make the membrane more fluid (Fig. 3-4). These include high temperature, lipids with shorter chains (double bonds. The shorter lipids and the m-double bonds cause the occurrence of holes (packing defects). 

The fluidity of lipid bilayers permits dynamic interactions among membrane proteins 25... 

The fluidity of lipid bilayers permits dynamic interactions among membrane proteins. For example, the interactions of a neurotransmitter or hormone with its receptor can dissociate a transducer protein, which in turn will diffuse to interact with other effector proteins (Ch. 19). A given effector protein, such as adenylyl cyclase, may respond differently to different receptors because of mediation by different transducers. These dynamic interactions require rapid protein diffusion within the plane of the membrane bilayer. Receptor occupation can initiate extensive redistribution of membrane proteins, as exemplified by the clustering of membrane antigens consequent to binding bivalent antibodies [8]. In contrast to these examples of lateral mobility, the surface distribution of integral membrane proteins can be fixed by interactions with other proteins. Membranes may also be partitioned into local spatial domains consisting of networks... 

In the literature, one can find many more interesting MD studies concerning lipid bilayers with additives. In particular, a wealth of MD simulations of such systems is in the field of anaesthetics (for a review see [142]). Many anaesthetics tend to accumulate at the membrane/water interface, implying that their potencies are not related to their ability to cross the membrane. Instead, it seems to be more likely that their functioning is via binding to membrane receptors. Generally, they have an effect opposite to that of cholesterol, i.e. they increase the membrane fluidity and permeability. 

We should first emphasize that viscosity is a macroscopic parameter which loses its physical meaning on a molecular scale. Therefore, the term microviscosity should be used with caution, and the term fluidity can be alternatively used to characterize, in a very general way, the effects of viscous drag and cohesion of the probed microenvironment (polymers, micelles, gels, lipid bilayers of vesicles or biological membranes, etc.). 

The vast majority of biological membranes are in the liquid-crystalline phase. There are many experimental studies on model bilayer phase behavior [3]. Briefly, at low temperatures lipid bilayers form a gel phase, characterized by high order and rigidity and slow lateral diffusion. There is a main phase transition, as the temperature is increased, to the liquid-crystalline phase. The liquid-crystalline phase has more fluidity and fast lateral diffusion. 

Although an increase in membrane fluidity caused by anesthetic intercalation into the lipid bilayer was thought to result in general anesthesia, this theory was flawed in the following ways ... 

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