Membrane lipid bilayers proteins

Studies of the effect of permeant s size on the translational diffusion in membranes suggest that a free-volume model is appropriate for the description of diffusion processes in the bilayers [93]. The dynamic motion of the chains of the membrane lipids and proteins may result in the formation of transient pockets of free volume or cavities into which a permeant molecule can enter. Diffusion occurs when a permeant jumps from a donor to an acceptor cavity. Results from recent molecular dynamics simulations suggest that the free volume transport mechanism is more likely to be operative in the core of the bilayer [84]. In the more ordered region of the bilayer, a kink shift diffusion mechanism is more likely to occur [84,94]. Kinks may be pictured as dynamic structural defects representing small, mobile free volumes in the hydrocarbon phase of the membrane, i.e., conformational kink g tg ) isomers of the hydrocarbon chains resulting from thermal motion [52] (Fig. 8). Small molecules can enter the small free volumes of the kinks and migrate across the membrane together with the kinks. 

Figure 3 A hydrophobic permeant must negotiate through a complex series of diffu-sional and thermodynamic barriers as it penetrates into a cell. The lipid and protein compositions and charge distribution of the inner and outer leaflets of the membrane lipid bilayer can play limiting roles, particularly at the tight junction. Depending upon the permeant s characteristics, it may remain within the plasma membrane or enter the cytoplasm, possibly in association with cytosolic proteins, and partition into cytoplasmic membranes.

Alkyl chain heterogeneities cause cell membrane bilayers to remain in the fluid state over a broad temperature range. This permits rapid lateral diffusion of membrane lipids and proteins within the plane of the bilayer. The lateral diffusion rate for an unconstrained phospholipid in a bilayer is of the order of 1 mm2 s 1 an integral membrane protein such as rhodopsin would diffuse 40nm2 s 1. 

The structure and roles of membrane microdomains (rafts) in cell membranes are under intensive study but many aspects are still unresolved. Unlike in synthetic bilayers (Fig. 2-2), no way has been found to directly visualize rafts in biomembranes [22]. Many investigators operationally define raft components as those membrane lipids and proteins (a) that remain insoluble after extraction with cold 1% Triton X-100 detergent, (b) that are recovered as a low density band that can be isolated by flotation centrifugation and (c) whose presence in this fraction should be reduced by cholesterol depletion. 

Once synthesized several factors influence the particular leaflet of the membrane lipid bilayer where the lipids reside. One is static interactions with intrinsic and extrinsic membrane proteins which, by virtue of their mechanism of biosynthesis, are also asymmetric with respect to the membrane. The interaction of the cytoplasmic protein, spectrin with the erythrocye membrane has been the subject of a number of studies. Coupling of spectrin to the transmembrane proteins, band 3 and glycophorin 3 via ankyrin and protein 4.1, respectively, has been well documented (van Doit et al, 1998). Interaction of spectrin with membrane lipids is still somewhat conjectural but recent studies have characterized such interactions more precisely. O Toole et al. (2000) have used a fluorescine derivative of phosphatidylethanolamine to investigate the binding affinity of specttin to lipid bilayers comprised of phosphatidylcholine or a binary mixture of phosphatidylcholine and phosphatidylserine. They concluded on the basis... 

Many membrane proteins seem to be afloat in a sea of lipids. Like membrane lipids, these proteins are free to diffuse laterally in the plane of the bilayer and are in... 

Allen and Bevan (80) have applied the SMD technique to the study of reversible inhibitors of monoamine oxidase B, and this paper will be used as an example for discussion of the constant velocity SMD pulling method. They used the Gromacs suite of biomolecular simulation programs (18) with the united-atom Gromos 43al force field to parameterize the lipid bilayer, protein, and small-molecule inhibitors. The protein was inserted into their mixed bilayer composed of phosphatidyl choline (POPC) and phosphatidyl ethanolamine (POPE) lipids in a ratio known to be consistent for a mitochondrial membrane. Each inhibitor-bound system studied was preequilibrated in a periodic box of SPC water (20) with the simulations run using the NPT ensemble at 300 K and 1 atm pressure for 20 ns. Full atomic coordinates and velocities were saved in 200-ps increments giving five replicates for each inhibitor-bound system. A dummy atom was attached to an atom (the SMD atom shown in Fig. 7) of the inhibitor nearest to the... 

Cell membrane Lipid bilayer, containing surface proteins (peripheral proteins), proteins totally embedded in the membrane (intregal proteins), and glycoproteins partially embedded in the membrane Maintains ionic and chemical concentration gradients, cell-specific markers, intercellular communication, regulates cell growth and proliferation... 

Diffusion is the random movement of a particle because of an exchange of thermal energy with its environment. Membrane lipids and proteins participate in highly anisotropic translational and rotational diffusion motion. Translational diffusion in the plane of the membrane is described by the mean square lateral displacement after a time At (r ) = TD At. Lipid lateral diffusion coefficients in fluid phase bilayers are typically in the range Dj 10 to 10 cm /s (3). 

As stated on several occasions in the previous sections, electrons are delivered to bacterial and PSI-RC by electron carriers which can be isolated as water soluble homogeneous proteins, cytochromes of c type or plastocyanine. These carriers represent also the physiological electron acceptors for the 6/Cj complexes. It has been conceived, therefore, that these proteins can act as diffusable redox mediators between the different complexes, which in turn are thought to be laterally and independently mobile in the membrane lipid bilayer [219]. The location of these carriers would be the interface on one side of the asymmetrically arranged coupling membrane, namely towards the periplasmic space in bacteria (corresponding to the internal volume of chromatophores) or the inner lumen of thylakoids. 

These data suggested that carnosine can be drawn into the protein synthesis providing specific regulatory role directed to support of essential genes in active state and to increase cell viability. In agreement with such suggestion, it was found that addition of carnosine to cell cultures promotes their viability and stimulates synthesis of a number of proteins, particularly, vimentin, which takes part in interaction of cytoskeleton with membrane lipid bilayer [63]. 

Slater SJ, Kelley MB, Taddeo FJ, Ho C, Rubin E, Stubbs CD. The modulation of protein kinase C activity by membrane lipid bilayer structure. J Biol Chem 1994 269 4866 871. 

Fig. 5.3 Three-dimensional structure of rhodopsin. Two views of rhodopsin. A) The seven a-helices of the C protein-coupled receptor rhodopsin weave back and forth through the membrane lipid bilayer (yellow lines) from the extracellular environment (bottom) to the cytoplasm (top). The chromophore 11-cis retinal (yellow) is nested among the transmembrane helices. B) View into the membrane plane from the cytoplasmic side of the membrane. Roman numerals indicate numbered helices.

Figure 1. Dose-response diagram for the effect of ichfan on micro viscosity of the erythrocyte (A), and of the cell of Ehrlich ascitic carcinoma (B). Probe I (light) (2,2,6,6-tetramethyl-4-capryloyl-oxypiperidin-l-oxyl) is localized in the surface layer of the membrane lipid bilayer Probe II (dark) (5,6-benzo-2,2,6,6-tetramethyl-l,2.3,4-tetrahydro-y-carbolin-3-oxyl) in the deep near-protein sites of lipids.

Proposed features of the interaction between the prothrombinase complex and a membrane lipid bilayer.Ky and K2 are the kringle domains of prothrombin, and EGFl and EGF2 are the two epidermal growth factor units of factor X. Prothrombin and factor form a heterodimer complex harbored within the membrane protein factor Va- The proposed interaction between prothrombin and factor X involves hydrophobic interactions between two helices and bridging by a ion between two Gla residues. The N-terminal Gla residues attach the heterodimer complex to the phospholipid surface. Figure kindly provided by C. C. F. Blake. 

Proteins and a lipid bilayer. Proteins are found in membranes, either spanning the membrane (transmembrane proteins), buried in the membrane (integral membrane proteins), or attached to the membrane surface (peripheral membrane proteins), as shown from top... 

The spectrin cytoskeleton is connected to the membrane lipid bilayer by ankyrin, which interacts with (3-spectrin and the integral membrane protein, band 3. Band 4.2 helps to stabilize this connection. Band 4.1 anchors the spectrin skeleton with the membrane by binding the integral membrane protein glycophorin C and the actin complex, which has bound multiple spectrin dimers. 

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