Lipid phases complex formation

FIG. 15 Cellular entry and intracellular kinetics of the cationic lipid-DNA complexes. Cationic lipid-DOPE liposomes form electrostatic complexes with DNA, and, in this case, also transferrin (Tf) is incorporated. Cellular uptake by endoc5dosis and endosomal acidification can be blocked with cytochaiasin B and bafilomycin Aj, respectively. DNA is proposed to be released at the level of endosomal wall after fusion of the carrier lipids with endosomal bilayer. This process is facilitated by the formation of inverted hexagonal DOPE phase as illustrated in the lower corner on the right. After its release to the C5doplasm DNA may enter the nucleus. (From Ref. 253. By permission of Nature Publishing Group.)... 

Direct initiation by lower valence states (M" ] of metals proceeds through formation of activated complexes with O2 (23, 45)—mostly via inner sphere complexes. As free reduced metals react rapidly with oxygen (Reaction 6a), this mechanism is active primarily when chelators specifically stabilize the reduced metals. These reactions also proceed mostly facilely in nonpolar solvent (46), e.g., in hydrophobic lipid phases of membranes or in oils. 

Complex formation - up until now we have assumed that the various lipids did not interact with each other (ideal behaviour) or at least they did not interact stoichiometrically. However, stoichiometric complex formation is sometimes a possibility that complicates the phase diagrams, as will also be shown below. 

Observations of thermotropic phase transitions even in simple lipid mixtures are complicated by factors such as nonideal miscibility, coexistence of different phases under certain conditions, and specific interactions between lipids, leading to complex formation. A well-studied, yet incompletely understood, binary lipid mixture that exemplifies these difficulties is the one formed by phosphatidylcholine and cholesterol. 

Finally, we discuss the role of interlamellar water in lipid phase transitions. As shown in Fig. 36, the phase behavior of the lipid in the DMPE-water system is complex in the absence of freezable interlamellar water [21], Presumably, in a region of such low water content, the lipid bilayers exist as hydrated crystals containing only nonfreezable interlamellar water. However, with the appearance of freezable interlamellar water (curves d-m), the lipid phase transition comes to be characterized by a certain peak that is gradually shifted to lower temperatures with increasing water content and finally converges to a fixed temperature, generally ascribed to the gel-to-liquid crystal phase transition. Such phase behavior suggests that freezable interlamellar water is absolutely necessary for the formation of the gel phase of lipid-water systems. In this respect, another noticeable point is that the fixed peak of the gel-to-liquid crystal transition is obtained above a certain water content where a maximum uptake of the freezable interlamellar... 

With the use of valinomycin as a carrier across the bilayer lipid membranes, a number of works appeared devoted to its adsorption and complex formation with potassium salts at water-air and water-oil interfaces. In spite of the considerable efforts of scientists, these problems are far from being solved. Boguslavsky et al. studied the contact phenomena at the water-heptane interface in the presence of valinomycin and its complexes with K. They found the potential values to be abnormally high [11,113]. The physical nature of these potentials is not clear. They are either related to the bulk charge in the heptane phase or to the formation of submolecular structures at the interface. 

Since the effects of heavy metals increase the amount of free radicals in the lipid phase, not only do the rates of initiation and propagation reactions increase, but also the rate of termination reaction increases. Heavy metals therefore also change the composition of the reaction products. At high concentrations of free radicals, the termination reaction may dominate and metals then act as the inhibitors of autoxidation. Autoxidation reaction can also be inhibited by metals when they are present at higher concentrations. It is assumed that the reason is the oxidation and reduction of free hydrocarbon radicals to anions and cations by ions of Fe and Cu and the formation of complexes of free radicals. Other complexes are also formed with Co. All these reactions interrupt the radical chain autoxidation reaction. Reactions with Fe ions are given as examples. 

Membrane lipids exhibit complex polymorphism as a function of temperature. A balance of lipid phase structure is believed to result from interaction of lipids with other membrane components and solutes in the aqueous phase. In general, this balance results in a formation of a fluid lipid bilayer matrix. Phase separations of lipid from other membrane constituents can be driven by exposure of membranes to temperatures outside the normal growth temperature. These can be the creation of gel phase domains at low temperature or the formation of nonbilayer structures at high temperature. Both types of lipid phase separation are associated with functional changes in the membrane including loss of selective permeability barrier properties. 

The major role of lipids is not only the formation of a lipid bilayer which will act as a structural matrix for proteins and protein complexes but also the association with proteins and protein complexes to build up lipid-protein-complexes. The function of lipids in lipid-protein-complexes is probably to stabilize the activity and conformation of proteins and protein complexes on their own and in the membrane. That shows that lipids provide a hydrophobic environment in which proteins and protein complexes are embedded, in which they can interact with each other and with other membrane components and in which they can change their conformation. So the surrounding lipid phase is very important for the structure, function and activity of membrane proteins [1,2]. 

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]. 

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