Fluid lipid bilayer

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. 

In the bilayer membrane model of the 1980s, cell membranes were based largely on a fluid lipid bilayer in which proteins were embedded [149,150]. The bilayer was highly dynamic lipids and proteins could flex, rotate, and diffuse laterally in a two-dimensional fluid. Based on this, the enhancing mechanisms of absorption enhancers on transcellular routes have been clarified. In summary, most of the mechanisms are strongly associated with membrane fluidity. The fluidity is likely to be changed by the following factors. 

Previous investigators showed that patterned surfaces allow partitioning of one fluid lipid bilayer from the next.34-35 Molecules within an individual membrane are free to move... 

FIGURE 6.6. Schematic depiction of the screening assay for monitoring ligand-receptor interactions on a supported fluid lipid bilayer in the presence of a library of soluble inhibitors. Surface specific observation is achieved using TIRFM. 

Y. Cheng, N. Boden, R. J. Bushby, S. Clarkson, S. D. Evans, P. F. Knowles, A. Marsh, and R. E. Miles, Attenuated total reflection Fourier transform infrared spectroscopic characterization of fluid lipid bilayers tethered to solid supports, Langmuir 14, 893-844 (1998). 

J. T. Groves, N. Ulman, and S. G. Boxer, Micropatterning fluid lipid bilayers on solid supports Science 275, 651-653 (1997). 

Polymer electrolytes conduct cations by segmental motions of the polymer backbone that carry the cations from one complexation site to the next.60-62 Since this requires significant fluidity, the polymers are conductive only in the amorphous state, i.e. above the crystalline to gel transition temperature. For the bulk polymer of PHB, this temperature is in the range of 0° to 10 °C. Accordingly, single molecules of PHB dissolved in fluid lipid bilayers should be capable of considerable segmental motions at physiological temperatures. 

Bloom, M., Evans, E. and Mouritsen, O. G. (1991). Physical properties of the fluid lipid-bilayer component of cell membranes A perspective. Quart. Rev. Biophys. 24 293. 

The nonpolar hydrocarbon skeleton of cholesterol is embedded in the nonpolar interior of the cell membrane. Its rigid carbon skeleton stiffens the fluid lipid bilayer, giving it strength. Cholesterol s polar OH group is oriented toward the aqueous media inside and outside the cell. 

The central stmctural feature of almost all biological membranes is a continuous and fluid lipid bilayer that serves as the major permeability barrier of the cell or intracellular compartment (1) and as a scaffold for the attachment and organization of other membrane constituents (2, 3). In particular, peripheral membrane proteins are bound to the surface of lipid bilayers primarily by electrostatic and hydrogen-bonding interactions, whereas integral membrane proteins penetrate into, and usually span, the lipid bilayer, and are stabilized by hydrophobic and van der Waal s interactions with the lipid hydrocarbon chains in the interior of the lipid bilayer as well as by polar interactions... 

The viscous drag felt at the bilayer-water interface can be large when the bounding fluid viscosity approaches the viscosity of the membrane (53) or when the fluid lipid bilayer is associated with a rigid substrate (54). 

Vaz WLC, StUmpel J, Hallmann D, Gambacorta A, De Rosa M. Bounding fluid viscosity and translational diffusion in a fluid lipid bilayer. Eur. Biophys. J. 1987 15 111-115. 

Many questions pertaining to membrane processes in general and ligand/membrane receptor interactions in particular can be addressed by a novel model membrane system, i.e., polymer-supported or polymer-tethered lipid bilayers [12,14], The basic structural unit for this sensor platform is the tethered lipid bilayer membrane [16] displayed in Fig. 2D. The essential architectural elements of this supramolecular assembly include the solid support, e.g., an optical or electrical transducer (device), the polymeric tether system which provides the partial covalent and, hence, very stable attachment of the whole membrane to the substrate surface, and the fluid lipid bilayer, functionalized if needed by embedded proteins. 

Although the hydrophobic barrier created by the fluid lipid bilayer is an important feature of membranes, the proteins embedded within the lipid bilayer are equally important and are responsible for critical cellular functions. The presence of these membrane proteins was revealed by an electron microscopic technique called freeze-fracture. Cells are frozen to very cold temperatures and then fractured with a very fine diamond knife. Some of the cells are fractured between the two layers of the lipid bilayer. When viewed with the electron microscope, the membrane appeared to be a mosaic, studded with proteins. Because of the fluidity of membranes and the appearance of the proteins seen by electron microscopy, our concept of membrane structure is called the fluid mosaic model (Figure 18.13). 

THE NATURE OF THE PERMEABILITY BARRIER AND THE BASIC MECHANISM of ion permeation are understood only in the most general sense even though the first measurements of ionic flux across lipid bilayer membranes were conducted 25 years ago. Establishing a permeation mechanism is difficult because the fluid lipid bilayer is described in terms of average motions of... 

A fluid or at least partially fluid lipid bilayer is essential for cellular function. Abnormally high transition temperatures reflect abnormally crystalline membranes, and are associated with cell leakage, changes in active transport and the activities of some membrane-associated enzymes, prolonged generation times, eventual loss of viability, and even cell... 

Striking features are the low cholesterol content and the high content of unsaturated fatty acids (esp. C 22 6). This indicates a highly fluid lipid bilayer. In agreement with this is the finding that the rhodopsin molecules rotate freely and rapidly (rotation time 20 ysec) in the plane of the membrane (Brown, 1972 Cone,... 

Bloom M, Evans E, Mouritsen OG (1991) Physical properties of the fluid lipid-bilayer component of cell membranes a perspective. Quart Rev Biophys 24(3) 293-397 Killian JA, SaleminkI, de Planque MRR, Lindblom G, Koeppe II RE, Greathouse DV(1996) Induction of nonbilayer structures in diacylphosphatidylcholine model membranes by transmembrane a-helical peptides importance of hydrophobic mismatch and proposed role of tryptophans. Biochemistry 35(3) 1037-1045... 

Membrane lipids exhibit complex polymorphism as a function of temperature. A balance of lipid phase structure is believed to result from interaction of lipids with other membrane components and solutes in the aqueous phase. In general, this balance results in a formation of a fluid lipid bilayer matrix. Phase separations of lipid from other membrane constituents can be driven by exposure of membranes to temperatures outside the normal growth temperature. These can be the creation of gel phase domains at low temperature or the formation of nonbilayer structures at high temperature. Both types of lipid phase separation are associated with functional changes in the membrane including loss of selective permeability barrier properties. 

It is clear from a variety of spectroscopic techniques that biomembranes are dynamic not static structures. It is also known that certain membrane functions depend critically on the fluidity of the membrane lipids. Spin-labelled and fluorescent-labelled lipid probes are found to perform rotational motions in the nanosecond timescale in fluid lipid bilayers and membranes. For diffusive rotation the characteristic correlation times are given by the Debye equation (t = n V/kT) and correspond to effective viscosities in the range q 0.1-1 poise. A spin-labelled steroid analogue of cholesterol for instance rotates rapidly about its long... 

Membranes with a relatively high protein content frequently display a second component in the ESR spectra of lipid spin labels, in addition to the fluid lipid bilayer component discussed in the previous section. This component is best resolved with labels close to the end of the chain, since a large degree of averaged spectral anisotropy is available to detect any immobilization induced by the protein. The ESR spectra of the 16-SASL stearic acid spin label in acetylcholine receptor-rich membranes and in bilayers of the extracted lipids is given in Fig. 3.3. A motionally restricted spin label component is seen in the outer wings of the spectrum from the membranes which is not present in the spectrum from the lipids alone. 

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