Lipids, self-assembly into biological

Recently, a new class of inhibitors (nonionic polymer surfactants) was identified as promising agents for drug formulations. These compounds are two- or three-block copolymers arranged in a linear ABA or AB structure. The A block is a hydrophilic polyethylene oxide) chain. The B block can be a hydrophobic lipid (in copolymers BRIJs, MYRJs, Tritons, Tweens, and Chremophor) or a poly(propylene oxide) chain (in copolymers Pluronics [BASF Corp., N.J., USA] and CRL-1606). Pluronic block copolymers with various numbers of hydrophilic EO (,n) and hydrophobic PO (in) units are characterized by distinct hydrophilic-lipophilic balance (HLB). Due to their amphiphilic character these copolymers display surfactant properties including ability to interact with hydrophobic surfaces and biological membranes. In aqueous solutions with concentrations above the CMC, these copolymers self-assemble into micelles. 

The second example of a biological supermolecule is a cell membrane. As described in Chap. 4, a cell membrane consists mainly of a fluidic lipid bilayer containing proteins (Fig. 6.2). The Hpids are self-assembled into the bilayer structure and the proteins float within the Hpid bilayer. The whole structure is formed through self-assembly processes. 

Biological systems are made up of structured macromolecules of specific sequence (proteins, nucleic acids, polysaccharides) and of smaller molecules (lipids, etc.) that self-assemble into larger structures. 

In Chapter 3, we introduced the concept of the surfactant and discussed how molecules with hydrophobic and hydrophilic sections will self-assemble into lyotropic phases in aqueous solution. The stability of a specific phase depends on molecular shape and concentration in the solvent. In the discussions that follow, we focus on the phase behavior of a simplified model membrane containing only lipids, even though the real cell membrane consists of a complex mbcture of many different varieties of lipids, sterols, and membrane proteins. Figure 6.3 shows molecular structures for some common lipid molecules found in the cell membrane. For a detailed description of the cell membrane, I recommend The Structure of Biological Membranes as further reading. ... 

Plate 29 Structure of membrane proteins. Membrane peptides often self assemble into controlled oligomerie forms to make molecular selective channels whose structure can be very difficult to resolve at the molecular level by most methods, although solid state NMR methods can make a contribution to their functional and structural description. Here the pentameric funnel-Hke bundle of the M2-peptide from the nicotinic acedy choline receptor has been resolved from NMR studies of oriented M2 peptides in lipid bilayers. The funnel has a wide mouth at the N-terminal, intracellular side of the pore. The pore lining residues has also been modelled and distances between residues in the channel estimated. The a-carbon backbone is in cyan, acidic residues in red and basic residues in blue, polar residues in yellow and lipophilic residues in purple. (Figure adapted from Opella et al., (1999) Nature St. Biology, 6 374-379). See Membranes Studied by NMR Spectroscopy. 

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. 

In order to achieve thorough fundamental understanding of bio molecular self-assembly, it is imperative to study ID tape-like self-assembly not only in bulk solution but also at interfaces. An example of a biologically relevant interface is that of the lipid bilayer. Systematic peptide-lipid studies have begun to offer an insight into the basic principles and mechanisms of interactions of selfassembling peptides with model lipid layers (Protopapa et al., 2006). 

Assembly of Proteins into Cell Membranes. The individual components of a biological membrane, after separation in the presence of a high concentration of detergent, still are able to associate into a membrane when the detergent is removed. However, such self-assembly of the normal constituents of a membrane fail to show asymmetry. This might be the result of a random insertion of integral proteins as the lipid... 

The simple model does allow an entry point into the study of self-assembly of multicomponent lipid systems, lateral phase separation (clustering), membrane asymmetry, and in particular how these relate to curvature through packing. These form a central class of problems in membrane biology. 

To demonstrate the existence of functional elements responsible for pore properties of channel proteins, peptides with sequences that represent such functional segments are synthesized and their ability to mimic the targeted biological activity is tested by incorporation of the peptides into lipid bilayers. This approach allows rapid determination of which presumed transmembrane helices may form functional channels. The peptides self-assemble in the membrane to generate conductive oligomers, presumably with hydrophobic surfaces that face the phospholipid and hydrophilic residues that fine the pore. Channels of different sizes (oligomeric number) result (37, 48). 

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