The hydrated synthetic lecithins, dimyristoyl and dipalmitoyllecithins, undergo two thermal transitions, a broad low enthalpy "pretransition" prior to the sharp first-order "chain-melting" transition. Both phospholipids exhibit the same temperature-dependent structural changes associated with the thermal pretransition. At low temperatures, below the pretransition, a one-dimensional lamellar lattice is observed. The hydrocarbon chains are fully extended and tilted with respect to the plane of the lipid bilayer. The hydrocarbon chain packing displays a temperature dependence and the angle of tilt of the hydrocarbon chains decreases with increasing temperature, reaching a minimum value of 30 degrees at the pretransition temperature of both lecithins. The pretransition is associated with a structural transformation from a one-dimensional lamellar to a two-dimensional monoclinic lattice consisting of lipid lamellae distorted by a periodic ripple. The hydrocarbon chains remain tilted in the temperature range intermediate between the pretransition and chain-melting transition. The cell parameters of this two-dimensional lattice exhibit a compositional dependence. The a parameter (proportional to the lamellar repeat distance) increases with increasing water content, while the b parameter (a measure of the ripple periodicity) decreases with increasing water content. At the chain-melting transition, the hydrocarbon chains of the phospholipid melt and assume a liquid-like conformation and the lattice reverts to one-dimensional lamellar. These structural changes observed for dimyristoyl- and dipalmitoyllecithins may be a common feature of all synthetic lecithins exhibiting a thermal pretransition. The appearance of the pretransition and accompanying two-dimensional may arise from specific interactions between the choline moiety of the polar head group and the structured water matrix surrounding it.

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Crystals of 1,2 dilauroyl-DL-phosphatidylethanolamine: acetic acid are monoclinic with a = 46.2, b = 7.77, c = 9.95 A, j3 = 92.00; space group P21/c. The structural analysis, based on the visual estimates of 1467 reflection intensities, was achieved by direct methods, and least squares analysis convergence was to R1 = 0.28. There are marked differences between the observed molecular conformation and those that have been predicted theoretically. The mean planes containing the lipid chains are essentially parallel to one another; the phosphodiester moiety has a double gauche conformation, while intermolecular hydrogen bonding modifies the conformation that could be anticipated for an isolated phosphatidylethanolamine molecule. The intermolecular packing produces the classical lipid bilayer structure, adjacent lipid bilayers being separated by acetic acid molecules of crystallization. The hydrocarbon chain packing can be considered either as a quasi-hexagonal type or as a complex orthorhombic subcell arrangement. One-dimensional electron density profiles across the lipid bilayer at increasing resolution clearly demonstrate the origin of features present on the low resolution profiles of both model and natural membranes.Phospholipids, glycolipids, and glycosphingolipids play a key structural and functional role in animal, plant, and bacterial cell membranes (1). Furthermore, phospholipids are important molecular components of the serum lipoproteins responsible for fat transport in the body (2) and of bile secreted by the liver where, together with bile salts, they solubilize cholesterol in a complex, aqueous, mixed micellar system (3).Although much information is available on the behavior of phospholipids in water (4, 5), the mutual interactions of different lipid classes, particularly phospholipid-cholesterol (6) (14), and sugars (15), which determine the different lipid classes, have been described. From this structural information, conformational analyses of different phospholipids have been made and, on this basis, the most likely structures have been predicted (12,16,17).In this paper we describe a single-crystal analysis of a phospholipid, the synthetic compound 1,2 dilauroyl-DL-z HsOJI-OCHsCHr-NHa O_ A knowledge of the molecular conformation and intermolecular packing of phosphatidylethanolamine and other phospholipids will allow a more detailed interpretation of the x-ray diffraction data derived from lipid-water, lipid-protein, and natural membrane systems.

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The structure and thermotropic properties of N-palmitoyl sphingomyelin (C16:0-SM) and its interaction with cholesterol and dipalmitoylphosphatidylcholine (DPPC) have been studied by differential scanning calorimetry (DSC) and X-ray diffraction methods. DSC of hydrated multi-bilayers of C16:0-SM shows reversible chain-melting transitions. On heating, anhydrous C16:0-SM exhibits an endothermic transition at 75 degrees C (delta H = 4.0 kcal/mol). Increasing hydration progressively lowers the transition temperature (TM) and increases the transition enthalpy (delta H), until limiting values (TM = 41 degrees C, delta H = 7.5 kcal/mol) are observed for hydration values > 25 wt % H2O. X-ray diffraction at temperatures below (29 degrees C) TM show a bilayer gel structure (d = 73.5 A, sharp 4.2 A reflection) for C16:0-SM at full hydration; above TM, at 55 degrees C, a bilayer liquid-crystal phase is present (d = 66.6 A, diffuse 4.6 A reflection). Addition of cholesterol to C16:0-SM bilayers results in a progressive decrease in the enthalpy of the transition at 41 degrees C, and no cooperative transition is detected at > 50 mol % cholesterol. X-ray diffraction shows no difference in the bilayer periodicity, position/width of the wide-angle reflections, or electron density profiles at 29 and 55 degrees C when 50 mol % cholesterol is present. Thus, cholesterol inserts into C16:0-SM bilayers progressively removing the chain-melting transition and changing the structural characteristics of the bilayer. DSC and X-ray diffraction data show that DPPC is completely miscible with C16:0-SM bilayers in both the gel and liquid-crystalline phases; however, 30 mol % C16:0-SM removes the pre-transition exhibited by DPPC.

The submitted manuscript has been authored by a contractor of the U.S. Government under contied No. W-31-104ENG-38. Accordingly. the U. S Government retains a nonexclusive, royalty-frw iicfinae to publlsh or reproduce the published form of thlc contribution, M allow othan to do lo, for U. S. Gowrnment purpoa.

Thermal analysis of human plasma low density lipoproteins reveals a broad reversible transition encompassing body temperature. The calorimetric and x-ray scattering data identify this transition as a cooperation, liquid-crystalline to liquid phase change involving the cholesterol esters in the lipoprotein. This behavior requires the presence of a region rich in cholesterol ester within the lipoprotein.

A B S T R A C T 95 individual human atherosclerotic lesions from 26 persons were classified into three groups under the dissecting microscope: fatty streaks, fibrous plaques, and gruel (atheromatous) plaques. Each lesion was isolated by microdissection, its lipid composition determined by chromatography, and the physical states of the lipids identified by polarizing microscopy and in some cases by X-ray diffraction. The composition of each lesion was plotted on the in vitro phase diagram of the major lipids of plaques: cholesterol, cholesterol ester, and phospholipid. The observed physical states were compared with those predicted by the location of the lipid composition on the phase diagram.The most severe lesions (gruel plaques) had an average lipid composition of cholesterol 31.5±1.9%, cholesterol ester 47.2±2.3%, and phospholipid 15.3±0.5%.Their compositions fell within the three-phase zone of the phase diagram, predicting the lipids to be separated into a cholesterol crystal phase, a cholesterol ester oily phase and a phospholipid liquid crystalline phase. In addition to the phospholipid liquid crystalline phase of membranes and myelin-like figures demonstrable by electron microscopy, polarizing microscopy revealed the other two predicted phases, isotropic cholesterol esterrich droplets and cholesterol crystals. X-ray diffraction studies verified the identity of the crystals as cholesterol monohydrate.Fibrous plaques also had an average lipid composition within the three-phase zone of the phase diagram. Polarizing microscopy revealed the presence of cholesterol monohydrate crystals and lipid droplets in all of these lesions; the droplets were predominately isotropic in 28 of the 31 fibrous plaques. Although these lesions had less free cholesterol and more cholesterol ester than gruel plaques, they were otherwise similar.Fatty streaks had compositions within both the twoand three-phase zones of the phase diagram. Compared with gruel plaques, the fatty streaks within the twophase zone, defined as "ordinary," had more cholesterol ester, less free cholesterol, a higher cholesteryl oleate/ cholesteryl linoleate ratio, a lower sphingomyelin/lecithin ratio, more anisotropic lipid droplets, and rare or no cholesterol crystals. Those lesions within the three-phase zone had many chemical and physical features intermediate between ordinary fatty streaks and gruel plaques. Moreover, 68% of these "intermediate" lesions had no cholesterol crystals by polarizing microscopy in spite of their compositions being within the three-phase zone, indicating the cholesterol ester oily phase or the phospholipid phase or both were supersaturated with cho-