Hydration Properties of Lamellar and Non-Lamellar Phases of Phosphatidylcholine and Phosphatidylethanolamine
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CPL CHEMISTRY AND Chemistry and Physics of Lipids PHYSICS OF LIPIDS ELSEVIER 81 (1996) 117 131 Hydration properties of lamellar and non-lamellar phases of phosphatidylcholine and phosphatidylethanolamine Thomas J. McIntosh* Department ~l Cell Biology, Duke Unicersity Medical Center, Durham, North Carolina 27710, USA Abstract Two of the most common phospholipids in biological membranes are phosphatidylcholine (PC) and phos- phatidylethanolamine (PE). Over a wide range of temperatures the PCs found in biological membranes form lamellar (bilayer) phases when dispersed in excess water, whereas PEs form either lamellar or hexagonal phases depending on their hydrocarbon chain composition. This paper details the hydration properties of lamellar and hexagonal phases formed by PCs and PEs, focusing on the energetics of hydration of these phases. For the hexagonal phase, the energy of bending the lipid monolayer is a critical term, with other contributions arising from the energies of hydrating the lipid headgroups and filling voids in the interstices in the hydrocarbon region. For the lamellar phase of PC, the water content is determined by a balance between the attractive van der Waals pressure and repulsive hydration and entropic (steric) pressures. In the case of PE bilayers, recent experiments demonstrate the presence of an additional strong, short-range attractive interaction, possibly due to hydrogen-bonded water interactions between N ' H3 groups in one bilayer and the PO4 groups in the apposing bilayer. This additional attractive pressure causes apposing PE bilayers to adhere strongly and to imbibe considerably less water than PC bilayers. Keywords: Lamellar and hexagonal phases: Hydration pressure: Steric pressure; Hydrogen bonding: X-Ray diffraction 1. Introduction temperature ranges when dispersed in an aqueous phase [1,2]. However, other phospholipids can Biological membranes contain several classes of form non-bilayer (non-lamellar) phases in excess phospholipids. Many of these lipids, such as the water. In particular, the second most common most common membrane phospholipid, phos- membrane phospholipid, phosphatidylethanol- phatidylcholine (PC), form bilayers over wide amine (PE), can form either lamellar or hexagonal It phases depending on a number of factors, including temperature, water content, and the *Tel.: +1 919 684 8950: fax: + 1 919 684 3687. composition of the PE hydrocarbon chains [3--7]. (1009-3084/96/$15.00 <~ 1996 Elsevier Science Ireland Ltd. All rights reserved Pll S0009- 3084(96)02577-7 118 T.J. Mclntosh / Chemistry aml Ph v.si~'.~ ol Lipi~L~ S I (199(,) I 17 I.~ I The presence in membranes of lipids that tend Tartar [14] considered micelle tbrmation by to form non-lamellar phases has long intrigued paraffin salts and found that the shape of the many membrane biophysicists. Numerous theo- micelle depended on the fully extended length of retical and experimental investigations have con- the hydrocarbon chain and the area occupied per sidered the role of these lipids in membrane polar headgroup. Tanford [15,16] considered am- structure and dynamics, as well as a variety of phiphiles with two chains, such as phospholipids, membrane activities such as enzymatic reactions and pointed out that the value of area per and membrane fusion. Many of these studies are molecule is lower ['or bilayers than lbr micelles reviewed in other articles in this special issue. This and that bilayers can accommodate a limitless review focuses on how diacyl phospholipids which number of chains without requiring a change in form non-lamellar phases impact the fundamental molecular area. Israelachvili and colleagues interactions between surfaces in water. Specifically [17,18] stressed the importance of molecular shape we compare and contrast the hydration properties on lipid organization. They argued that bilayers and intersurface interactions of lamellar and are formed by cylindrically shaped lipid molecules hexagonal phases containing the two most thor- (excluded area in the headgroup region approxi- oughly studied phospholipids, PC and PE. The mately the same as in the chain region), whereas factors determining the energetics of dehydrating non-lamellar phases are formed by cone-shaped bilayer and hexagonal phases are discussed. Em- molecules. Specifically, lipid molecules with the phasis is given to recent experiments that have headgroup area smaller than the hydrocarbon revealed the mechanisms by which PE affects the chain area would be expected to form inverted hydration of membrane bilayers. hexagonal phases. This shape hypothesis is sup- ported by the observation that highly unsaturated 2. Phase properties of PE and PC PEs and long-chained PEs (which would be ex- pected to have large volumes in their hydrocarbon Membrane phospholipids contain a mixture of regions) form hexagonal phases, whereas short- fatty acid chains, varying in length and number of chained PEs form lamellar phases [3,4], Further double bonds. In general, diacyl PCs found in experimental support for this hypothesis has been biological membranes form lamellar phases in obtained with several electrically neutral lipid spe- excess water at physiological temperatures [1,2]. cies with systematically varying headgroup vol- Diacyl PEs with short (12 carbons per chain) umes [19]. In addition, the incorporation of lipids saturated chains also tend to form lamellar phases with polyethylene glycol (PEG) covalently at- at physiological temperatures [4,8], whereas PEs tached to their headgroups stabilizes the bilayer with unsaturated chains tend to form hexagonal phase in DOPE/cholesterol mixtures, at least II phases [3-7,9,10]. For fully hydrated lipids, the partly because of the complementary 'inverted transition temperature for the lamellar-to-hexago- cone' shape of the PEG-lipids [20]. nal phase transition depends on the hydrocarbon Gruner and colleagues [21 23] noted that the chain length and number of double bonds per concept of molecular shape ignores other factors chain. For example, fully hydrated dioleoylphos- such as headgroup charge and intermolecular hy- phatidylethanolamine (DOPE), which has hydro- drogen-bonding. This is an important consider- carbon chains containing 18 carbons with one ation in terms of the PEs, because it has been double bond, has a lamellar-to-hexagonal phase shown that at high pH, where the PE headgroup transition near 5°C [11,12]. is negatively charged, the hexagonal phase is con- The factors that determine the phase behavior verted to single-walled vesicles [24]. Moreover, of particular lipids have been investigated for intermolecular hydrogen bonding is thought to many years (see review by Seddon [13]). Here we play a role in the structure and properties of PE consider some of the basic principles that are phases [7,10,25 31]. Gruner and colleagues important to the hydration properties of hexago- [22,23] view the transitions between mesomorphic nal and lamellar phases. phases with curved interfaces in terms of a "corn- T.J. Mclntosh / Chemistry and Physics q[ Lipids 81 (1996} 117 13l 119 petition between the elastic energy of bending the 23 for eggPC and greater than 12 for eggPE. The interfaces and energies resulting from the con- water contents of lamellar phases of a variety of straints of interfacial separation'. They argue that PCs and PEs have been obtained by several tech- the propensity of a lipid system to form a non- niques, including NMR [38,39], differential scan- lamellar phase depends on its spontaneous radius ning calorimetry [40-43] and X-ray diffraction of curvature, which represents the minimum elas- [4,8,33,40,44-60]. As tabulated in a recent review tic free energy state of the lipid monolayer with [61], there is some variability in the results from respect to bend. Thus, the spontaneous radius of different laboratories and from lipids with differ- curvature represents the radius of surface that ent hydrocarbon compositions and chain linkages. these lipids would form in the absence of inter- However, from these many measurements, two monolayer packing constraints [32]. Evidence fa- general and important conclusions can be voring the spontaneous radius of curvature model reached: (1) for both PC and PE the water con- comes from the work of Leventis et al. [32] who tents are higher for liquid-crystalline than for gel analyzed a number of PE analogs with alkylated phases, and (2) PC absorbs more water than PE headgroups and Gruner et al. [33] who studied in either the liquid-crystalline or gel phase. For N-methylated PEs. Leventis et al. [32] found a example, in a particularly detailed and careful correlation between the hexagonal lattice repeat analysis, Nagle and Wiener [57] find that the dimension, which is a measure of the spontaneous maximum number of water molecules per lipid radius of curvature, and the lamellar-to-hexagonal molecule are: 14 and 23 for gel and liquid-crys- phase transition temperature of these lipids and talline phase dipalmit oylphosphatidylcholine Gruner et al. [33] found that both the hexagonal (DPPC), respectively, and 6 and 9 fl)r gel and lattice repeat dimension and the stability of the liquid-crystalline phase dilauroylphos- lamellar phase increase with increasing headgroup phatidylethanolamine (DLPE), respectively. methylation. Epand and Epand [34] have used A number of investigations have probed the titration calorimetry to measure the heats of reac- reasons for the differences in hydration of gel and tion between bilayers and lysoPC (which has a liquid-crystalline PEs and