Membrane Structure Model

Mauritz and Moore provided a state-of-the-art review of structure investigation on Nafion membranes. Devanathan reported recent progress in understanding Nafion.  

Perfluorosulfonated membranes have a microscopic phase-separated structure with hydrophobic regions and hydrophilic domain. Hydrophobic regions provide the mechanical support and hydrophilic ionic domains provide proton transport channel. Many morphological models for PFSA have been developed based on SAXS and wide-angle x-ray scattering (WAXS) experiments of the membranes. However, because of the random chemical structure of the PFSA copolymer, morphological variation with water content and complexity of coorganized crystalline and ionic domains, limited characteristic detail proved by the SAXS and WAXS experiments, the structure of the PFSl has been still subject of debate. Here, a brief description of seven membrane structure models is provided. 

Local-order model Based on the observation from SANS experiments on Nation samples and excellent agreanent between the theoretical and 

FIGURE 2.9 Core-shell model for Nafion membrane. (From Fujimura, M. et al., 

Discrete sandwich Haubold ef al. proposed a variation of the lamellar model, discrete sandwich. The rectangle with a sandwich structure was chosen as the structure element. The sandwich consists of shell (the outer portion) and core (inner liquid portion). The former consists of the side chains and the latter consists of water/methanol molecules. These structural elements were proposed to be juxtaposed in a linear fashion and random distributed inside the membrane. The core thickness c, total shell thickness s, and their lateral dimensions a and b are calculated, a and b is between 15 and 45 A, and the total thickness (cH-i ) is about 60 A. 

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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... 

In 1972, S. J. Singer and G. L. Nicolson proposed the fluid mosaic model for membrane structure, which suggested that membranes are dynamic structures composed of proteins and phospholipids. In this model, the phospholipid bilayer is a fluid matrix, in essence, a two-dimensional solvent for proteins. Both lipids and proteins are capable of rotational and lateral movement. 

FIGURE 9.6 The fluid mosaic model of membrane structure proposed by S. J. Singer and G. L. Nicolsou. In this model, the lipids and proteins are assumed to be mobile, so that they can move rapidly and laterally in the plane of the membrane. Transverse motion may also occur, but it is much slower. 

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... 

Figure 41-7. The fluid mosaic model of membrane structure. The membrane consists of a bimolecu-lar lipid layer with proteins inserted in it or bound to either surface. Integral membrane proteins are firmly embedded in the lipid layers. Some of these proteins completely span the bilayer and are called transmembrane proteins, while others are embedded in either the outer or inner leaflet of the lipid bilayer. Loosely bound to the outer or inner surface of the membrane are the peripheral proteins. Many of the proteins and lipids have externally exposed oligosaccharide chains. (Reproduced, with permission, from Junqueira LC, Carneiro J Basic Histology. Text Atlas, 10th ed. McGraw-Hill, 2003.)...

THE FLUID MOSAIC MODEL OF MEMBRANE STRUCTURE IS WIDELY ACCEPTED... 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

L. G. Reevaluating equilibrium and kinetic binding parameters for lipophilic drugs based on a structural model for drug interaction with biological membranes. 

Our knowledge of biological membrane ultrastructure has increased considerably over the years as a result of rapid advances in instrumentation. Although there is still controversy over the most correct biological membrane model, the concept of membrane structure presented by Davson and Danielli of a lipid bilayer is perhaps the one best accepted [12,13]. The most current version of that basic model, illustrated in Fig. 7, is referred to as the fluid mosaic model of membrane structure. This model is consistent with what we have learned about the existence of specific ion channels and receptors within and along surface membranes. 

Mason, R. R Rhodes, D. G. Herbette, L. G., Reevaluating equilibrium and kinetic binding parameters for lipophilic drugs based on a structural model for drug interaction with bilogical membranes, J. Med. Chem. 34, 869-877 (1991). 

Fig. 1 Solid-state NMR structure analysis relies on the 19F-labelled peptides being uniformly embedded in a macroscopically oriented membrane sample, (a) The angle (0) of the 19F-labelled group (e.g. a CF3-moiety) on the peptide backbone (shown here as a cylinder) relative to the static magnetic field is directly reflected in the NMR parameter measured (e.g. DD, see Fig. 2c). (b) The value of the experimental NMR parameter varies along the peptide sequence with a periodicity that is characteristic for distinct peptide conformations, (c) From such wave plot the alignment of the peptide with respect to the lipid bilayer normal (n) can then be evaluated in terms of its tilt angle (x) and azimuthal rotation (p). Whole-body wobbling can be described by an order parameter, S rtlo. (d) The combined data from several individual 19F-labelled peptide analogues thus yields a 3D structural model of the peptide and how it is oriented in the lipid bilayer...

FLUID-MOSAIC MODEL of membrane structure. Proteins and lipids that are embedded in the lipid bilayer diffuse rapidly in the plane of the membrane. 

Myelin in situ has a water content of about 40%. The dry mass of both CNS and PNS myelin is characterized by a high proportion of lipid (70-85%) and, consequently, a low proportion of protein (15-30%). By comparison, most biological membranes have a higher ratio of proteins to lipids. The currently accepted view of membrane structure is that of a lipid bilayer with integral membrane proteins embedded in the bilayer and other extrinsic proteins attached to one surface or the other by weaker linkages. Proteins and lipids are asymmetrically distributed in this bilayer, with only partial asymmetry of the lipids. The proposed molecular architecture of the layered membranes of compact myelin fits such a concept (Fig. 4-11). Models of compact myelin are based on data from electron microscopy, immunostaining, X-ray diffraction, surface probes studies, structural abnormalities in mutant mice, correlations between structure and composition in various species, and predictions of protein structure from sequencing information [4]. 

All of the above considerations have sometimes led to a too rigid picture of the membrane structure. Of course, the mentioned types of fluctuations (protrusions, fluctuations in area per molecule, chain interdigitations) do exist and will turn out to be important. Without these, the membrane would lack any mechanism to, for example, adjust to the environmental conditions or to accommodate additives. Here we come to the central theme of this review. In order to come to predictive models for permeation in, and transport through bilayers, it is necessary to go beyond the surfactant parameter approach and the fluid mosaic model. 

The formalism sketched above has been used in the literature in more or less the same detail by many authors [87-92]. The predicted membrane structure that follows from this strategy has one essential problem the main gel-to-liquid phase transition known to occur in lipid membranes is not recovered. It is interesting to note that one of the first computer models of the bilayer membrane by Marcelja [93] did feature a first-order phase transition. This author included nematic-like interactions between the acyl tail, similar to that used in liquid crystals. This approach was abandoned for modelling membranes in later studies, because this transition was (unfortunately) lost when the molecules were described in more detail [87]. 

Leermakers, F. A. M. and Kleijn, J. M. (2004). Molecular modelling of biological membranes. Structure and permeation properties. In Physicochemical Kinetics and Transport at Biointerfaces, eds. van Leeuwen, H. P. and Koster, W., Vol. 9, IUPAC Series on Analytical and Physical Chemistry of Environmental Systems, Series eds. Buffle, J. and van Leeuwen, H. P., John Wiley Sons, Ltd, Chichester, pp. 15-111. 

Menziani, M.C., Fanelli, F., Cocchi, M. and De Benedetti, P.G. (1996) The heuristic-direct approach to quantitative structure-activity relationship analysis of ligand-G protein coupled receptor complexes, in Membrane Protein Models Experiment, Theory and Speculation (ed. J. Findlay), Bios Science Publications, pp. 113-131. 

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