Cholesterol phospholipid bilayers

Liposomes are artificial structures primarily composed of phospholipid bilayers exhibiting amphiphilic properties. Other molecules, such as cholesterol or fatty acids also may be included in the bilayer construction. In complex liposome morphologies, concentric spheres or sheets of lipid bilayers are usually separated by aqueous regions that are sequestered or compartmentalized from the surrounding solution. The phospholipid constituents of liposomes consist of hydrophobic lipid tails connected to a head constructed of various glycerylphosphate... 

Bolard J, Seigneuret M, Boudet G. Interaction between phospholipid bilayer membranes and the polyene antibiotic amphotericin B lipid state and cholesterol content dependence. Biochim Biophys Acta 1980 599 280. 

Deuterium NMR studies of chain and headgroup deuterated phospholipid bilayers and phospholipid—cholesterol mixtures... 

MD simulations have provided a unique molecular description of cholesterol-phospholipid interactions [31]. Atomistic simulations have succeeded in reproducing the condensing effect of cholesterol on phospholipid bilayers [32-34], With atomistic detail, many properties can be determined, such as the effect of cholesterol on lipid chain ordering or on hydrogen bond formation. Other simulations have focused on the interaction of cholesterol and SM [35-37], Aittoniemi et al. [38] showed that hydrogen bonding alone cannot explain the preferential interaction between cholesterol and SM compared to cholesterol and POPC. 

Hofsass, C., Lindahl, E., Edholm, O. Molecular dynamics simulations of phospholipid bilayers with cholesterol. Biophys. J. 2003, 84, 2192-206. 

Mitchell, D.C., Litman, B.J. Effect of cholesterol on molecular order and dynamics in highly polyunsaturated phospholipid bilayers. Biophys. J. 1998, 75, 896-908. 

The plasma membrane, a phospholipid bilayer in which cholesterol and protein molecules are embedded. The bottom layer, which faces the cytoplasm, has a slightly different phospholipid composition from that of the top layer, which faces the external medium. While phospholipid molecules can readily exchange laterally within their own layer, random exchange across the bilayer is rare. Both globular and helical kinds of protein traverse the bilayer. Cholesterol molecules tend to keep the tails of the phospholipids relatively fixed and orderly in the regions closest to the hydrophilic heads the parts of the tails closer to the core of the membrane move about freely. This model is not believed to apply to blood or lymph capillaries. (Reprinted with permission from Bretscher MS. The molecules of the cell membrane. Sci Am 1985 253 104. Copyright 1985 by Scientific American, Inc. All rights reserved.)... 

Our present ideas about the nature of biological membranes, which are so fundamental to all biochemical processes, are based on the Singer-Nicholson mosaic model. This model of the membrane is based on a phospholipid bilayer that is, however, asymmetrical. In the outside monolayer, phosphatidylcholine (lecithin) predominates, whereas the inner monolayer on the cytoplasmic side is rich in a mixture of phos-phatidylethanolamine, phosphatidylserine, and phosphatidylinositol. Cholesterol molecules are also inserted into the bilayer, with their 3-hydroxyl group pointed toward the aqueous side. The hydrophobic fatty acid tails and the steran skeleton of cholesterol... 

Many of the proteins of membranes are enzymes. For example, the entire electron transport system of mitochondria (Chapter 18) is embedded in membranes and a number of highly lipid-soluble enzymes have been isolated. Examples are phosphatidylseiine decarboxylase, which converts phosphatidylserine to phosphatidylethanolamine in biosynthesis of the latter, and isoprenoid alcohol phosphokinase, which participates in bacterial cell wall synthesis (Chapter 20). A number of ectoenzymes are present predominantly on the outsides of cell membranes.329 Enzymes such as phospholipases (Chapter 12), which are present on membrane surfaces, often are relatively inactive when removed from the lipid environment but are active in the presence of phospholipid bilay-ers.330 33 The distribution of lipid chain lengths as well as the cholesterol content of the membrane can affect enzymatic activities.332... 

As the final outer stratum comeum is formed the phospholipid bilayer deteriorates and intercellular lipid layers are formed.k l These contain principally ceramides, cholesterol, and free fatty acids. Some sphingolipids are covalently attached to proteins.3... 

The amount of disorder in the fatty acid side chains in a phospholipid bilayer, as a function of temperature. The side chains become much more disordered as the temperature increases through the 7m. The solid curve represents a bilayer that does not contain cholesterol the dotted curve, a bilayer with the same phospholipid plus about 25% cholesterol. The amount of random, disorderly motion of the fatty acid chains can be measured quantitatively by deuterium- or l3C-NMR. At any given temperature, the disorder is greater near the tips of the chains (toward the middle of the bilayer) than it is close to the head-groups. 

We have not yet said much about the second major constituent of eukaryotic membrane lipids, cholesterol. Cholesterol broadens the melting transition of the phospholipid bilayer (see fig. 17.20). Below the Tm, cholesterol disorders the membrane because it is too bulky to fit well into the neatly packed arrangement of the fatty acid chains that is favored at low temperatures. Above the Tm, cholesterol restricts further disordering because it is too large and inflexible to join in the rapid fluctuations of the chains. If the amount of cholesterol in a phospholipid bilayer is increased to about 30%, roughly the amount in the plasma membranes of typical animal cells, the melting transition becomes so broad as to be almost undetectable. 

Qeveral recent investigations using various physicochemical methods have provided convincing evidence to support the contention that the basic structure of most biological membranes consists of a phospholipid bilayer (1,2,3, 4). Studies on phospholipid model membranes can therefore be expected to yield relevant information on the role played by phospholipids in determining the characteristic properties of biological membranes (5). One important aspect of this problem concerns the mechanisms of interaction between the phospholipids and other membrane constituents such as cholesterol, proteins, and different inorganic... 

In all our linewidth studies the width of the central peak was measured—i.e., the linewidth obeying Equation lib. In Ref. 45 we reported 23Na linewidth studies on a lamellar mesophase containing egg-yolk lecithin. The effect of cholesterol on the linewidth was investigated, and we found that with increasing cholesterol content in the phospholipid bilayers a marked reduction in the linewidth was observed. In accordance with similar investigations for simple soap-alcohol-water lamellar mesophases (42, 43) this is interpreted as a partial release of... 

The Singer and Nicholson (13) model for the plasma membrane, which now receives much support, is basically a smectic liquid crystal consisting of one bilayer of phospholipid (Figure 4a). The phospholipid bilayer contains cholesterol at a concentration which depends on cell type. Embedded in the lipid liquid crystal he protein molecules. Some of these protein molecules transverse the entire lipid bilayer and communicate both with the inside and the outside of the cells. Some of these may... 

Another significant component of many liposome preparations is cholesterol. In natural cell membranes, cholesterol makes up about 10—50% of the total lipid on a molar basis. For liposome preparation, it is typical to include a molar ratio of about 50% cholesterol in the total lipid recipe. The addition of cholesterol to phospholipid bilayers alters the properties of the resultant membrane in important ways. As it dissolves in the membrane, cholesterol orients itself with its polar hydroxyl group pointed toward the aqueous outer environment, approximately even, in a three-dimensional sense, with the glyceryl backbone of the bilayer s phosphodiglyceride components (Fig. 337). Structurally, cholesterol is a rigid component in membrane construction, not having the same freedom of movement that the fatty acid tails of... 

The solubilization phenomenon, which refers to the dissolution of normally insoluble or only slightly soluble compounds in water caused by the addition of surfactants, is one of the most striking effects encountered for surfactant systems. Solubilization is of considerable physico-chemical interst, such as in discussion of the structure and dynamics of micelles and of the mechanism of enzyme catalysis, and has numerous practical applications, such as in detergency, in pharmaceutical preparations and in micellar catalysis. In biology, solubilization phenomena are most significant, e.g., cholesterol solubilization in phospholipid bilayers and fat solubilization in fat digestion and transport. 

---