Lipid bilayers, interactions with

How do proteins and the lipid bilayer interact with each other in membranes ... 

The artificial lipid bilayer is often prepared via the vesicle-fusion method [8]. In the vesicle fusion process, immersing a solid substrate in a vesicle dispersion solution induces adsorption and rupture of the vesicles on the substrate, which yields a planar and continuous lipid bilayer structure (Figure 13.1) [9]. The Langmuir-Blodgett transfer process is also a useful method [10]. These artificial lipid bilayers can support various biomolecules [11-16]. However, we have to take care because some transmembrane proteins incorporated in these artificial lipid bilayers interact directly with the substrate surface due to a lack of sufficient space between the bilayer and the substrate. This alters the native properties of the proteins and prohibits free diffusion in the lipid bilayer [17[. To avoid this undesirable situation, polymer-supported bilayers [7, 18, 19] or tethered bilayers [20, 21] are used. 

Cationic lipids interact electrostatically and form stable complexes (lipoplexes) with the polyanionic nucleic acids. The structure of most lipoplexes is a multi-lamellar sandwich in which lipid bilayers alternate with layers of DNA strands [16, 62-64] (Fig. 20). Although infrequent, nonlamellar structures have also been found. The free energy gain upon lipoplex formation was shown to be essentially of entropic nature resulting from the counterion release and macromolecule dehydration [65, 66]. 

The role of thermal fluctuations for membranes interacting via arbitrary potentials, which constitutes a problem of general interest, is however still unsolved. Earlier treatments G-7 coupled the fluctuations and the interaction potential and revealed that the fluctuation pressure has a different functional dependence on the intermembrane separation than that predicted by Helfrich for rigid-wall interactions. The calculations were refined later by using variational methods.3 8 The first of them employed a symmetric functional form for the distribution of the membrane positions as the solution of a diffusion equation in an infinite well.3 However, recent Monte Carlo simulations of stacks of lipid bilayers interacting via realistic potentials indicated that the distribution of the intermembrane distances is asymmetric 9 the root-mean-square fluctuations obtained from experiment were also shown to be in disagreement with this theory.10... 

Line shape analysis of the static 31P NMR spectra and its corresponding CSA values have been successfully used to study the perturbation effect induced by proteins. 31P data for PLs bilayers interacting with antimicrobial peptide (AMP) magainin-2, aurein-3,3, incorporated into structures of supramolecular lipid assemblies such as toroidal pores and thinned bilayers have been reported.90 Various types of PL systems (l-palmitoyl-d3i-2-oleoyl-s -glycero-3-phosphotidylcholine... 

The main stabilizing feature of biological membranes is hydrophobic interactions among the molecules in the lipid bilayer. The phospholipids in the lipid bilayer orient themselves so that their polar head groups interact with water. Proteins in the lipid bilayer interact favorably in their hydrophobic milieu because they typically have hydrophobic amino acid residues on their outer surfaces. 

Lipids are not covalently bound in membranes but rather interact dynamically to form transient arrangements with asymmetry both perpendicular and parallel to the plane of the lipid bilayer. The fluidity, supermolecular-phase propensity, lateral pressure and surface charge of the bilayer matrix is largely determined by the collective properties of the complex mixture of individual lipid species, some of which are shown in Fig. 8.1. Lipids also interact with and bind to proteins in stiochiometric amounts affecting protein structure and function. The broad range of lipid properties coupled with the dynamic organization of lipids in membranes multiplies their functional diversity in modulating the environment and therefore the function of membrane proteins. 

A recent account by Matile et al. [62] can be considered as the first experimental example of the use of anion-tt interactions for the design of a synthetic anion channel. Matile and co-workers report the design, synthesis, and evaluation of jt-acidic, shape-persistent ohgo-(p-phenylene)-N,N-naphthalenediimide (0-NDI) rods that can transport anions across lipid bilayer membranes with a rare selectivity Cl" > F" > Br" > I" and a substantial anomalous mole fraction effect. DFT calculations revealed a global quadrupole moment Qzz =+ 19.4 B for a model NDI. By comparison with... 

For reasons discussed in detail by Singer (1971) the current concept of membrane structure is that of a lipid bilayer intercalated with proteins, referred to as the fluid mosaic model (Fig. 11). It is based primarily on thermodynamic arguments (Tanford, 1973) concerned with the fact that it is energetically favorable for the ionic portion of an amphipathic substance to be in direct contact with water while its hydrophobic tail is sequestered from water and interacts with other nonpolar molecules. The role of hydrophobic interactions in protein conformation was first emphasized by Kauzman (1959). It is not our purpose here to review the area of membrane structure (see articles by Singer, 1971 Tanford, 1973), but certain points are important to the discussion of effector functions. 

Protems can be physisorbed or covalently attached to mica. Another method is to innnobilise and orient them by specific binding to receptor-fiinctionalized planar lipid bilayers supported on the mica sheets [15]. These surfaces are then brought into contact in an aqueous electrolyte solution, while the pH and the ionic strength are varied. Corresponding variations in the force-versus-distance curve allow conclusions about protein confomiation and interaction to be drawn [99]. The local electrostatic potential of protein-covered surfaces can hence be detemiined with an accuracy of 5 mV. 

There has been considerable interest in the simulation of lipid bilayers due to their biological importance. Early calculations on amphiphilic assemblies were limited by the computing power available, and so relatively simple models were employed. One of the most important of these is the mean field approach of Marcelja [Marcelja 1973, 1974], in which the interaction of a single hydrocarbon chain with its neighbours is represented by two additional contributions to the energy function. The energy of a chain in the mean field is given by ... 

Whereas the main challenge for the first bilayer simulations has been to obtain stable bilayers with properties (e.g., densities) which compare well with experiments, more and more complex problems can be tackled nowadays. For example, lipid bilayers were set up and compared in different phases (the fluid, the gel, the ripple phase) [67,68,76,81]. The formation of large pores and the structure of water in these water channels have been studied [80,81], and the forces acting on lipids which are pulled out of a membrane have been measured [82]. The bilayer systems themselves are also becoming more complex. Bilayers made of complicated amphiphiles such as unsaturated lipids have been considered [83,84]. The effect of adding cholesterol has been investigated [85,86]. An increasing number of studies are concerned with the important complex of hpid/protein interactions [87-89] and, in particular, with the structure of ion channels [90-92]. 

Baumgartner and coworkers [145,146] study lipid-protein interactions in lipid bilayers. The lipids are modeled as chains of hard spheres with heads tethered to two virtual surfaces, representing the two sides of the bilayer. Within this model, Baumgartner [145] has investigated the influence of membrane curvature on the conformations of a long embedded chain (a protein ). He predicts that the protein spontaneously localizes on the inner side of the membrane, due to the larger fluctuations of lipid density there. Sintes and Baumgartner [146] have calculated the lipid-mediated interactions between cylindrical inclusions ( proteins ). Apart from the... 

Lipids in model systems are often found in asymmetric clusters (see Figure 9.8). Such behavior is referred to as a phase separation, which arises either spontaneously or as the result of some extraneous influence. Phase separations can be induced in model membranes by divalent cations, which interact with negatively charged moieties on the surface of the bilayer. For example, Ca induces phase separations in membranes formed from phosphatidylserine (PS)... 

Bilayer phase transitions are sensitive to the presence of solutes that interact with lipids, including multivalent cations, lipid-soluble agents, peptides, and proteins. 

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