Membrane bilayer model

In 1980 it was pointed out that the prolamellar body is a perfect example of a Cp structure [4]. (Later, more detailed, analyses have revealed that it may also be a Cd structure cf. section 7.2.) Following work on the structure of cubic phases, it was also realised that two-dimensional analogues are possible. This in turn suggested that a phase transition involving changes in the intrinsic curvature of membranes might be possible [29, 30]. Such a mechanism has far reaching implications. Clear evidence for such transitions between bilayer conformations has been reported [9]. This membrane bilayer model will be described below. 

Hydrated bilayers containing one or more lipid components are commonly employed as models for biological membranes. These model systems exhibit a multiplicity of structural phases that are not observed in biological membranes. In the state that is analogous to fluid biological membranes, the liquid crystal or La bilayer phase present above the main bilayer phase transition temperature, Ta, the lipid hydrocarbon chains are conforma-tionally disordered and fluid ( melted ), and the lipids diffuse in the plane of the bilayer. At temperatures well below Ta, hydrated bilayers exist in the gel, or Lp, state in which the mostly all-trans chains are collectively tilted and pack in a regular two-dimensional... 

With the adequacy of lipid bilayer membranes as models for the basic structural motif and hence for the ion transport barrier of biological membranes, studies of channel and carrier ion transport mechanisms across such membranes become of central relevance to transport across cell membranes. The fundamental principles derived from these studies, however, have generality beyond the specific model systems. As noted above and as will be treated below, it is found that selective transport... 

A further partihon system based on the use of liposomes, and commercialized under the name Transil [110, 111], has shown its utiUty as a UpophiUcity measure in PBPK modeling [112]. Fluorescent-labeled liposomes, called fluorosomes, are another means of measuring the rate of penetration of small molecules into membrane bilayers [113, 120]. Similarly, a colorimetric assay amenable to HTS for evaluating membrane interactions and penetrahon has been presented [116]. The platform comprises vesicles of phospholipids and the chromahc Upid-mimehc polydiacetylene. The polymer undergoes visible concentrahon-dependent red-blue transformahons induced through interactions of the vesicles with the studied molecules. 

The most successful continuum description of membrane elasticity, dynamics, and thermodynamics is based on the smectic bilayer model (for examples of different versions and applications of this approach see Ref. 76-82 and references therein). We introduce this model in conjunction with the question of membrane undulations. 

It is well known that the permeabilities across biological membranes and model lipid bilayers strongly depend on both the degree of lipid chain packing in the membranes... 

Baumgartner, A. (1994). Asymmetries of a curved bilayer model membrane, J. Chem. Phys., 101, 9060-9062. 

Several mechanistic models have also been proposed to elucidate how the P-gp transporter translocates substrates across cellular membranes. In the vacuum cleaner model, which seems the most probable, the compounds partition into the membrane bilayer and then P-gp extracts the substrates from the inner (cytosolic) membrane leaflet and releases them through a protein channel into the extracellular medium (Figure 16.1) [7,14,17]. 

Figure 16.1 Schematic representation of a vacuum cleaner model drug partitions into the membrane bilayer, flips across the lipid core, accesses the TMDs from the inner membrane leaflet and is released through a protein channel into the extracellular medium.

Figure 3. Possible mechanisms of actions of Bcl-2 members. Two prevailing models through which Bcl-2 membas trigger cytochrome c release have been suggested. In both models phospholipids in the bilayer stnicture either individually and/or collectively induce a conformational change in Bcl-2 members, allowing them to insert into the outer mitochondrial membrane. In model 1 proapoptotic proteins destabilize the outer mitochondrial membrane, oligomerize and form channels through which cytochrome c and other proteins of the intermembrane space can escape.BcI-2 proteins such as Bax or tBid act in concert with other proteins of the BcI-2 family to form channels. In model 2 Bcl-2 members such as Bax interact with residoit proteins in the outer membrane (OM) such as the voltage-dependent anion...

Baatz JE, Elledge B, Whitsett JA. Surfactant protein SP-B induces ordering at the surface of model membrane bilayers. Biochemistry 1990 29(28) 6714-6720. 

It is possible that quite different molecular architectures may occur in membranes from different sources. Current research may result in a much more dramatic revision or complete rejection of the bilayer model for some membranes, especially in such systems as mitochondria (30) and chloroplasts (2). However, it is also possible that structural differences are only variations on the basic theme of the bilayer, from myelin at one extreme to mitochondria or chloroplasts on the other. One must not readily reject the fundamentals of the Danielli concept, especially in view of the present inadequate knowledge of the properties of phospholipids in water. Clearly the molecular architecture of membranes is speculative, but most aspects of the problem are amenable to direct experimental test by the new physical techniques. A consistent model for biological membranes will emerge quickly. 

Figure 18-8 Stereoscopic ribbon diagrams of the chicken bc1 complex (A) The native dimer. The molecular twofold axis runs vertically between the two monomers. Quinones, phospholipids, and detergent molecules are not shown for clarity. The presumed membrane bilayer is represented by a gray band. (B) Isolated close-up view of the two conformations of the Rieske protein (top and long helix at right) in contact with cytochrome b (below), with associated heme groups and bound inhibitors, stigmatellin, and antimycin. The isolated heme of cytochrome c, (left, above) is also shown. (C) Structure of the intermembrane (external surface) domains of the chicken bcx complex. This is viewed from within the membrane, with the transmembrane helices truncated at roughly the membrane surface. Ball-and-stick models represent the heme group of cytochrome cy the Rieske iron-sulfur cluster, and the disulfide cysteines of subunit 8. SU, subunit cyt, cytochrome. From Zhang et al.105...

Lipid bilayer (see Bilayer). Model for the structure of the cell membrane based on the hydrophobic interaction between phospholipids. 

A series of derivatives of tetramic acid were synthesized and complexed to cop-per(II) (Cu-TA,Fig.21) [176,177]. At 300 MHz,the Rt value of Cu-aTA is 0.073 0.004 mM 1 s-1 and the R2 value is 0.091 0.006 mM 1 s 1 [176]. The ability of the Cu-TA derivatives to cross membranes was measured using defolliculated Xeno-pus laevis oocytes as model cells. Using MR microscopy techniques, Cu-aTA, Cu-bTA, Cu-cTA and Cu-eTA were all found to cross into the cytoplasm of the cells [177]. Additionally, atomic absorption spectroscopy revealed the presence of Cu-dTA and Cu-fTA, suggesting that while the complexes failed to cross the cell membrane that they were stored in the membrane-bilayer. Liquid chromatography experiments demonstrated that Cu-aTA crosses membranes intact [176]. 

Fortunately, most of the perturbations that can occur in complex biological membranes upon interaction with drug molecules can be studied and simulated in vitro and quantified by available physicochemical techniques, using as a model artificial membranes (bilayers, liposomes), which are readily created. 

In some milk fat globules, small aqueous compartments are located beneath the membrane bilayer, which have been termed cytoplasmic crescents (Huston and Patton, 1990). Whether or not this cytoplasmic inclusion provides some benefit is unknown. Yet, as this aqueous compartment is protected from the bulk serum phase by the MFGM, constituents located therein are presumably afforded some protection, at least initially, from gastric hydrolysis. Huston and Patton (1990) found crescents in all samples of milk they examined, and they were more prevalent in human (7.3% of globules), than in bovine (1% of globules) milk. Furthermore, there was considerable individual and diurnal variation. The structure of a cytoplasmic inclusion, surrounded by an intact plasma membrane on one side and a fat globule surface on the other, may allow certain labile constituents to be protected until they reach their proper site of bioactivity. At this point it is not known whether the crescents have a purpose or are simply the result of inefficiencies in the secretion process. As it is possible to isolate milk preparations enriched in cytoplasmic crescents, there is an opportunity to determine the nature of the materials found within. This unusual biocompartment may prove to be a model of food structure for biodelivery. 

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