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Zero Spontaneous Curvature and Its Effects on Lamellar Phase Morphology and Vesicle Size Distributions

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Zero Spontaneous Curvature and Its Effects on Lamellar Phase Morphology and Vesicle Size Distributions 2474 Langmuir 2006, 22, 2474-2481 Zero Spontaneous Curvature and Its Effects on Lamellar Phase Morphology and Vesicle Size Distributions Bret A. Coldren, Heidi Warriner, Ryan van Zanten, and Joseph A. Zasadzinski* Department of Chemical Engineering, UniVersity of California, Santa Barbara, California 93106-5080 Eric B. Sirota Exxon Research and Engineering Company, Corporate Strategic Research, Route 22 East, Annandale, New Jersey 08801 ReceiVed September 7, 2005. In Final Form: January 2, 2006 Equimolar mixtures of dodecyltrimethylammonium chloride (DTAC) and sodium octyl sulfonate (SOSo) show a vesicle phase at >99 wt % water and a single, fluid lamellar phase for water fractions below 80 wt %. This combination is consistent with the bilayer bending elasticity κ ≈ kBT and zero bilayer spontaneous curvature. Caille´ line shape analysis of the small-angle X-ray scattering from the lamellar phase shows that the effective κ depends on the lamellar d spacing consistent with a logarithmic renormalization of κ, with κo ) (0.8 ( 0.1)kBT. The vesicle size distribution determined by cryogenic transmission electron microscopy is well fit by models with zero spontaneous curvature to give (κ + (κj/2)) ) (1.7 ( 0.1)kBT, resulting in κj)(1.8 ( 0.2)kBT. The positive value of κj and the lack of spontaneous curvature act to eliminate the spherulite defects found in the lamellar gel phases found in other catanionic mixtures. Current theories of spontaneous bilayer curvature require an excess of one or more components on opposite sides of the bilayer; the absence of such an excess at equimolar surfactant ratios explains the zero spontaneous curvature. Introduction bilayer. To stabilize a bilayer, κ > 0, but κj>0 for surfaces that It is no surprise that oppositely charged surfactants mix in a prefer hyperbolic shapes (saddle-shaped surfaces in which the < highly nonideal way and in fact are able to form structures such centers of curvature are on opposite sides of the surface, c1c2 j< as unilamellar vesicles that are not found in other surfactant 0) and κ 0 for surfaces that prefer elliptical shapes (spheres, mixtures.1 The range of self-assembled microstructures in ellipsoids, etc. in which the centers of curvature are on the same > mixtures of cationic and anionic surfactants also includes small side of the surface, c1c2 0). For a chemically and physically 3-5 spherical micelles, cylindrical or wormlike micelles, and other symmetric bilayer, the spontaneous curvature c0 equals 0. 2 Hence, a single-component bilayer cannot have a nonzero lamellar and L3 phases. The vesicle phases discussed here form spontaneously with no external energy input, and some vesicle spontaneous curvature. Theory suggests that it is necessary for phases have been observed for well over a decade, suggesting the bilayer or its local environment to be chemically asymmetric 5 at least metastable equilibrium. for spontaneous curvature to exist. The fundamental questions remain as to why vesicles form in Purely entropically stabilized vesicles have a low bending ≈ mixtures of oppositely charged surfactants and, once formed, constant (κ kBT, where kB is the Boltzmann constant), so the whether they are at thermodynamic equilibrium. The formation enthalpic bending contribution to the free energy is small and stability of any surfactant aggregate depends on whether compared to the mixing entropy. Unilamellar vesicles are that aggregate represents the global minimum in free energy for stabilized against aggregation and formation of multilamellar a given composition, and there are different approaches to liposomes by both the entropy of mixing and the steric repulsion describing the energetics of these mixtures. Translational entropy between bilayers caused by Helfrich undulations. The Helfrich favors many unilamellar vesicles over a smaller number of undulation repulsion is a consequence of bilayer thermal multilamellar liposomes. To examine the enthalpic part of the fluctuations, which are damped when bilayers come into contact; free energy, it is often useful to start with a mechanical description this causes the bilayer entropy to be reduced and leads to a 6 of the properties of the bilayer.3-5 In this case, the elastic energy repulsive interaction. For bilayers in a lamellar phase of repeat spacing d and membrane thickness δ, the Helfrich undulation of a bilayer is described by the two principle curvatures c1 and repulsion is c2. For spherical vesicles, c1 ) c2 ) 1/R, in which R is the vesicle radius. To terms second order in curvature, the free energy of 3,4 2 2 a bilayer, per unit area, is 3π (kBT) E ) (2) und 128 2 E 1 κ(d - δ) ) κ(c + c - 2c )2 + κjc c (1) A 2 1 2 0 1 2 (For free bilayer or vesicles, (d - δ) is replaced by the interbilayer in which κ is the bending modulus, κj is the saddle splay or (2) Kaler, E. W.; Herrington, K. L.; Iampietro, D. J.; Coldren, B.; Jung, H. Gaussian modulus, and c0 is the spontaneous curvature of the T.; Zasadzinski, J. A. In Mixed Surfactant Systems, 2nd ed.; Abe, M., Scamehorn, J., Eds.; Marcel Dekker: New York, 2005; pp 298-338. * To whom correspondence should be addressed. E-mail:gorilla@ (3) Frank, F. C. Discuss. Faraday Soc. 1958, 25,19-28. engineering.ucsb.edu. Phone: 805-893-4768. Fax: 805-893-4731. (4) Helfrich, W. Z. Naturforsch. 1973, 28C, 693-703. (1) Kaler, E. W.; Murthy, A. K.; Rodriguez, B. E.; Zasadzinski, J. A. N.Science (5) Safran, S. A.; Pincus, P. A.; Andelman, D. Science 1990, 248, 354-356. 1989, 245, 1371-1374. (6) Helfrich, W. Z. Naturforsch. 1978, 33A, 305-315. 10.1021/la052448p CCC: $33.50 © 2006 American Chemical Society Published on Web 02/09/2006 Lamellar Phase Morphology and Vesicle Size Langmuir, Vol. 22, No. 6, 2006 2475 distance.) The repulsive undulation interaction can overwhelm the van der Waals attraction between bilayers (which is also proportional to (d - δ)-2) when κ is small, leading to a net repulsive interaction between bilayers and hence stable unila- mellar vesicles, especially when combined with electrostatic repulsion in charged systems.7-9 Enthalpically stabilized vesicles, however, require nonzero spontaneous curvature and a larger value of the bending constant (κ > kBT). The curvature energy of forming a multilamellar liposome with many layers far from the optimal curvature is prohibitively high. In this case, the vesicles are narrowly distributed around a preferred size set by the spontaneous curvature.8,9 Spontaneous, apparently equilibrium vesicles with both narrow8-10 and broad size distributions1,2,11-15 in aqueous mixtures of a wide range of mixtures of cationic and anionic (catanionic) surfactants have been characterized by a variety of experimental techniques including small-angle neutron, X-ray, and light scattering and cryo and freeze-fracture transmission electron microscopy. The most common cationic surfactant used has been an alkytrimethylammonium bromide or tosylate, (e.g., cetyltrimethylammonium bromide (CTAB) or tosylate (CTAT)), whereas the common anionic surfactants are the sodium alkyl sulfates (e.g., sodium octyl (SOS), decyl sulfate (SDS), or dodecylbenzene sulfonate (SDBS)), which may have either a branched or comb structure. The phase diagrams of mixtures of these surfactants typically show two vesicle lobes, which are roughly symmetric on either side of the equimolar line at high water fractions (Figure 1A). One vesicle phase has a net excess of anionic surfactant, whereas the other has a net excess of cationic Figure 1. (a) Partial phase diagram of CTAT/SDBS/water at 25 °C. surfactant. For most catanionic mixtures, an insoluble precipitate Typical of most catanionic mixtures, the phase diagram is roughly forms at equimolar anion-to-cation ratios. At lower water symmetric about the equimolar line. Two vesicle lobes (V) are found fractions, two lamellar gel phases (MLV in Figure 1A) are found at high water fractions, one with an excess of CTAT and the other that are turbid and viscoelastic because of a highly defected, with an excess of SDBS. An insoluble precipitate forms along the spherulite texture; the lamellar gel phases are also located roughly equimolar line. The symmetric MLV phases are onionlike multi- 16 lamellar spherulites with no excess water that form a lamellar gel symmetrically about the equimolar line. These gels are similar similar to DMPC/pentanol/polymer lipid gels.17-19 Not indicated to lamellar gels of dimyristoylphosphatidylcholine, pentanol, and are micellar phases at either extreme of the surfactant mixing ratio. - poly(ethylene glycol) lipids17 19 and show a transition at lower (b) Partial phase diagram of DTAC/SOSo/water at 25 °C. M water fractions to a fluid, flat bilayer phase.16,20 A simple defect- represents spherical micelle phases, R represents a viscous rodlike based theory of this structural progression requires that κ ≈ kBT micelle phase, and V represents unilamellar vesicles. Instead of two and that c * 0.17-19 Cryo-TEM analysis of the vesicle size symmetric lobes, both the vesicle and lamellar phase occur along 0 the equimolar line. The lamellar phase consists of flat stacks at all distributions and Caille´ line shape analysis of the small-angle compositionssno MLV spherulite phase is observed. (7) Herve´, P.; Roux, D.; Bellocq, A.-M.; Nallet, F.; Gulik-Krzywicki, T. J. 16,19,21-23 ≈ - X-ray scattering confirm that κ kBT for all of the Phys. II 1993, 8, 1255 1270. 16,20 (8) Jung, H. T.; Coldren, B.; Zasadzinski, J. A.; Iampietro, D. J.; Kaler, E. W. catanionic systems studied thus far. This shows that surfactant Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 1353-1357. mixing can lead to low bending constants24 and is consistent (9) Jung, H. T.; Lee, Y. S.; Kaler, E. W.; Coldren, B.; Zasadzinski, J. A. Proc. with the entropic stabilization of spontaneous vesicles and the Natl. Acad. Sci. U.S.A.
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