Curvature-induced membrane-structural

It is now well established that proteins can induce phase transitions in lipid membranes, resulting in new structures not found in pure lipid-water systems (c/. section 5.1). However, this property is not peculiar to proteins the same effect can be induced by virtually any amphiphilic molecule. Depending on the structure and nature of proteins, their interactions with lipid bilayers can be manifested in very different ways. We may further assume that the role of proteins in the biogenesis of cubic membranes is analogous to that in condensed systems, and lipids are necessary for the formation of a cubic membrane. This assumption is supported by studies of membrane oxidation, which induce a structure-less proteinaceous mass [113]. However, the existence of a lipid bilayer by itself does not guarantee the formation of a cubic membrane, as proteins may also play an essential role in setting the membrane curvature. In this context, note that the presence of chiral components e.g. proteins) may induce saddle-shaped structures characteristic of cubic membranes. (This feature of chiral packings has been discussed briefly in section 4.14)... 

Facial amphiphilic peptides are another class of facial amphiphiles, which play an important rote in many biological processes involving lipid bilayer membranes. Because of the large surface area of the amphiphilic domains, they are prone to interact with the hydrophiUc/hydrophobic interface of lipid bilayers, which is necessary to assist in membrane fusion or transmembrane pore formation. In the case of pore-forming antibiotics, the peptides are often relatively small (between 25 and 100 amino acids) and the entire peptide becomes facially amphiphilic on folding into the secondary structure. In the case of membrane fusion or curvature-inducing proteins only the peptide fragment, which interacts with the bilayer membrane, is facially amphiphilic. 

Fig. 2 Schematic representation of potential changes in integral membrane protein structure that could be imposed by a micellar environment (left hand side of each panel), compared to the native structure in bilayers (right). Possible distortions include (a) micelle-induced curvature in the TM helix or amphipathic helix (b) monomeric detergent molecules bound to a solvent-exposed region, in this case an aqueous cavity close to the micelle surface (c) altered relative orientations of amphipathic vs TM helices (d) loss of tilt relative to other TM segments. In this scenario hydrophobic mismatch between the TM helix and micelle are minimized by distortions in micelle structure that allow hydrophobic protein surfaces to remain in the hydrophobic phase. In the bilayer environment hydrophobic mismatch induces tilt, favoring a non-zero inter-helical crossing angles...

Many electron spin resonance (ESR) studies of different systems have shown that phase separation in lipid layers may lead to a domain-like lateral structure. The area of domain formation can be extended over several hundred A. In this connection the charge-induced domain formation in biomembranes is of special interest for the medicinal chemist. Especially the addition of Ca to negatively charged lipids leads to domain formation. Each lipid component is expected to have a characteristic spontaneous curvature. The Ca - induced domains lead to protrusions in the membrane plane. The lateral variation in the concentration in the plane of the membrane would then lead to a parallel variation in... 

Figure 12 exhibits that incorporation of cholesterol to dication artificial amphiphile induced a transformation of the aggregated structure from monolayer lamellae to monomolecular liposome (multilamellar liposome or single-walled vesicles). The vesicles are 100 200 nm in diameter and their membrane thickness is at least 5 20 nm. It is suspected that cholesterol molecules are mostly located in the outer half of the membrane, thus creating curvature suitable for the vesicle formation. 

Although helpful, this schematic representation raises two issues. First, the plasma membrane also contains sphingolipids (inverted cones with 0 < P < 1/3) and cholesterol (cones with P = 1.21), and it is still assumed to adopt a bilayer structure. Second, the lipid composition of each leaflet of the plasma membrane is specific, and this transmembrane asymmetry induces a curvature that would not occur if all lipids were cylindrical. Solving these problems will help us to figure out how a plasma membrane is really organized at the lipid level. 

FIGURE 2.16 Lipid polymorphism of phosphatidylethanolamine inverted micelles and hexagonal Hn phases. Taper lipids such as phosphatidylethanolamine (PE) have a higher propensity to form micellar rather than bilayer structures. In the plasma membrane, PE can induce curvature effects and hexagonal (Hn) phase formation. 

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