Abstract
Relationships between the permeability coefficient (PHA) and partition coefficient (K m/w) of acetic acid and the surface density of DMPC:cholesterol bilayers have been investigated. Permeability coefficients were measured in large unilamellar vesicles by NMR line broadening. Bilayer surface density, σ, was varied over a range of 0.5–0.9 by changing cholesterol concentration and temperature. The temperature dependence of PHA for acetic acid exhibits Arrhenius behavior with an average apparent activation energy (E a ) of 22±3 kcal/mole over a cholesterol mole fraction range of 0.00–0.40. This value is much greater than the enthalpy change for acetic acid partitioning between bulk decane and water (ΔH° = 4.8±0.8 kcal/mole) and the calculated E a (= 8.0 kcal/mole) assuming a “bulk phase” permeability model which includes the enthalpy of transfer from water to decane and the temperature dependence of acetic acid's diffusion coefficient in decane. These results suggest that dehydration, previously considered to be a dominant component, is a minor factor in determining E a . Values of 1n PHA decrease linearly with the normalized phospholipid surface density with a slope of κ = -12.4±1.1 (r = 0.90). Correction of PHA for those temperature effects considered to be independent of lipid chain order (i.e., enthalpy of transfer from water to decane and activation energy for diffusion in bulk hydrocarbon) yielded an improved correlation (κ = -11.7±0.5 (r = 0.96)). The temperature dependence of Km/w is substantially smaller than that for PHA and dependent on cholesterol composition. Values of 1n Km/w decrease linearly with the surface density with a slope of κ = -4.6±0.3 (r = 0.95), which is 2.7-fold smaller than the slope of the plot of 1n PHA vs. σ. Thus, chain ordering is a major determinant for molecular partitioning into and transport across lipid bilayers, regardless of whether it is varied by lipid composition or temperature.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Alger, J.R., Prestegard, J.H. 1979. Nuclear magnetic resonance study of acetic acid permeation of large unilamellar vesicle membranes. Biophys. J. 28:1–14
Antunes-Madeira, M.C., Madeira, V.M.C. 1984. Partition of parathion in synthetic and native membranes. Biochim. Biophys. Acta 778:49–56
Antunes-Madeira, M.C., Madeira, V.M.C. 1985. Partition of lindane in synthetic and native membranes. Biochim. Biophys. Acta 820:165–172
Bangham, A.D., Standish, M.M., Watkins, J.C. 1965. Diffusion of univalent ions across the lamellae of swollen phospholipids. J. Mol. Biol. 13:238–252
Bar-On, Z., Degani, H. 1985. Permeability of alkylamines across phosphatidylcholine vesicles as studied by 1H-NMR. Biochim. Biophys. Acta 813:207–212
Beschiaschvili, G., Seelig, J. 1992. Peptide binding to lipid bilayers. Nonclassical hydrophobic effect and membrane-induced pK shifts. Biochemistry 31:10044–10053
Bindslev, N., Wright, E.M. 1976. Effect of temperature on nonelectrolyte permeation across the toad urinary bladder. J. Membrane Biol., 29:265–288
Brahm, J. 1983. Permeability of human red cells to a homologous series of alphatic alcohols. J. Gen. Physiol. 81:283–304
Bresseleers, G.J.M., Goderis, H.L., Tobback, P.P. 1984. Measurement of the glucose permeation rate across phospholipid bilayers using small unilamellar vesicles. Effect of membrane composition and temperature. Biochim. Biophys. Acta 772:374–382
Cantor, R.S., Dill, K.A. 1986. Theory for the equation of state of phospholipid monolayers. Langmuir 2:331–337
Cohen, M.H., Turnbull, D. 1959. Molecular transport in liquids and glasses. J. Chem. Phys. 31:1164–1168
de Gier, J., Mandersloot, J.G., Hupkes, J.V., McElhaney, R.N., van Beek, W.P. 1971. On the mechanism of non-electrolyte permeation through lipid bilayers and through biomembranes. Biochim. Biophys. Acta 233:610–618
DeYoung, L.R., Dill, K.A. 1988. Solute partitioning into lipid bilayer membranes. Biochemistry 27:5281–5289
DeYoung, L.R., Dill, K.A. 1990. Partitioning of nonpolar solutes into bilayers and amorphous n-alkanes. J. Phys. Chem. 94:801–809
Diamond, J.M., Katz, Y. 1974. Interpretation of nonelectrolyte partition coefficients between dimyristoyl lecithin and water. J. Membrane Biol. 17:121–154
Diamond, J.M., Szabo, G., Katz, Y. 1974. Theory of nonelectrolyte permeation in a generalized membrane. J. Membrane Biol. 17:148–152
Fenske, D.B., Cullis, P.R. 1993. Acyl chain orientational order in large unilamellar vesicles: comparison with multilamellar liposomes: a 2H and 31P nuclear magnetic resonance study. Biophys. J. 64:1482–1491
Finkelstein, A. 1976. Water and nonelectrolyte permeability of lipid bilayer membranes. J. Gen. Physiol. 68:127–135
Franks, N.P. 1976. Structural analysis of hydrated egg lecithin and cholesterol bilayers. I. X-ray diffraction. J. Mol. Biol. 100:345–358
Glasoe, P.K., Long, F.A. 1960. Use of glass electrodes to measure acidities in deuterium oxide. J. Phys. Chem. 64:188–190
Hope, M.J., Bally, M.B., Webb, G., Cullis, P.R. 1985. Production of large unilamellar vesicles by a rapid extrusion procedure. Characterization of size distribution, trapped volume and ability to maintain a membrane potential. Biochim. Biophys. Acta 812:55–65
Huang, C., Wheeldon, L., Thompson, T.E. 1964. The properties of lipid bilayer membranes separating two aqueous phases: formation of a membrane of simple composition. J. Mol. Biol. 8:148–160
Huang, C.-H., Sipe, J.P., Chow, S.T., Martin, R.B. 1974. Differential interaction of cholesterol with phosphatidylcholine on the inner and outer surfaces of lipid bilayer vesicles. Proc. Natl. Acad. Sci. USA 71:359–362
Katz, Y., Diamond, J.M. 1974a. Nonsolvent water in liposomes. J. Membrane Biol. 17:87–100
Katz, Y., Diamond, J.M. 1974b. Thermodynamic constants for non-electrolyte partition between dimyristoyl lecithin and water. J. Membrane Biol. 17:101–120
Korman, S., LaMer, V.K. 1936. Deuterium exchange equilibria in solution and the quinhydrone electrode. J. Amer. Chem. Soc. 58:1396–1403
Lieb, W.R., Stein, W.D. 1986. Simple diffusion across the membrane bilayer. In: Transport and Diffusion across Cell Membranes W.D. Stein, editor, pp. 69–112. Academic Press, Orlando
Magin, R.L., Niesman, M.R. 1984. Temperature dependent permeability of large unilamellar liposomes. Chem. Phys. Lipids 34:245–256
Marcelja, S. 1974. Chain order in in liquid crystals. II. Structure of bilayer membranes. Biochim. Biophys. Acta 367:165–176
Marqusee, J.A., Dill, K.A. 1986. Solute partitioning into chain molecule interphases: Monolayers, bilayer membranes, and micelles. J. Chem. Phys. 85:434–444
McIntosh, T.J., Simon, S.A., MacDonald, R.C. 1980. The organization of n-alkanes in lipid bilayers. Biochim. Biophys. Acta 597:445–463
Miller, K.W., Hammond, L., Porter, E.G. 1977. The solubility of hydrocarbon gases in lipid bilayers. Chem. Phys. Lipids 20:229–241
Nagle, J.F. 1993. Area/lipid of bilayers from NMR. Biophys. J. 64:1476–1481
Newman, G.C., Huang, C.-H. 1975. Structural studies on phosphatidylcholine-cholesterol mixed vesicles. Biochemistry 14:3363–3370
Olson, F., Hunt, C.A., Szoka, F.C., Vail, W.J., Papahadjopoulous, D. 1979. Preparation of liposomes of defined size distribution by extrusion through polycarbonate membranes. Biochim. Biophys. Acta 557:9–23
Orbach, E., Finkelstein, A. 1980. The nonelectrolyte permeability of planar lipid bilayer membranes. J. Gen. Physiol. 75:427–436
Overton, E. 1899. Ueber die allgemeinen osmotischen Eigenschaften der Zelle, ihre vermutlichen Ursachen und ihre Bedeutung für die Physiologie. Vjschr. Naturforsch. Ges. Zürich 44:88
Peitzsch, R.M., McLaughlin, S. 1993. Binding of acylated peptides and fatty acids to phospholipid vesicles: Pertinence to myristoylated proteins. Biochemistry 32:10436–10443
Peters, R., Beck, K. 1983. Translational diffusion in phospholipid monolayers measured by fluorescence microphotolysis. Proc. Natl. Acad. Sci. USA 80:7183–7187
Piette, L.H., Anderson, W.A. 1959. Potential energy barrier determination for some alkyl nitrates by nuclear magnetic resonance. J. Chem. Phys. 30:899–908
Pope, J.M., Walker, L.W., Dubro, D. 1984. On the ordering of n-alkane and n-alcohol solutes in phospholipid bilayer model membrane systems. Chem. Phys. Lipids 35:259–277
Rand, R.P., Parsegian, V.A. 1989. Hydration forces between phospholipid bilayers. Biochim. Biophys. Acta 988:351–376
Redwood, W.R., Haydon, D.A. 1969. Influence of temperature and membrane composition on the water permeability of lipid bilayers. J. Theoret. Biol. 22:1–8
Sada, E., Katoh, S., Terashima, M., Kawahara, H., Katoh, M. 1990. Effects of surface charges and cholesterol content on amino acid permeabilities of small unilamellar vesicles. J. Pharm. Sci. 79:232–235
Scheibel, E.G. 1954. Liquid diffusivities. Ind. Eng. Chem. 46:2007–2008
Seelig, J., Ganz, P. 1991. Nonclassical hydrophobic effect in membrane binding equilibria. Biochemistry 30:9354–9359
Seelig, A., Seelig, J. 1974. The dynamic structure of fatty acyl chains in a phospholipid bilayer measured by deuterium magnetic resonance. Biochemistry 13:4839–4845
Stein, W.D. 1986. Transport and Diffusion Across Cell Membranes. Academic Press, Orlando
Stockton, G.W., Polnaszek, C.F., Tulloch, A.P., Hasan, F., Smith, I.C.P. 1976. Molecular motion and order in single-bilayer vesicles and multilamellar dispersions of egg lecithin and lecithin-cholesterol mixtures. A deuterium nuclear magnetic resonance study of specifically labeled lipids. Biochemistry 15:954–966
Subcznski, W.K., Hyde, J.S., Kusumi, A. 1991. Effect of alkyl chain unsaturation and cholesterol intercalation on oxygen transport in membranes: A pulse ESR spin labeling study. Biochemistry 30:8578–8590
Todd, A.P., Mehlhorn, R.J., Macey, R.I. 1989a. Amine and carboxylate spin probe permeability in red cells. J. Membrane Biol. 109:41–52
Todd, A.P., Mehlhorn, R.J., Macey, R.I. 1989b. Amine spin probe permeability in sonicated liposomes. J. Membrane Biol. 109:53–64
Turnbull, D., Cohen, M.H. 1970. On the free-volume model of the liquid-glass transition. J. Chem. Phys. 52:3038–3041
Walter, A., Gutknecht, J. 1986. Permeability of small nonelectrolytes through lipid bilayer membranes. J. Membrane Biol. 90:207–217
Weisz, K., Grobner, G., Mayer, C., Stohrer, J., Kothe, G. 1992. Deuteron nuclear magnetic resonance study of the dynamic organization of phospholipid/cholesterol bilayer membranes; molecular properties and viscoelastic behavior. Biochemistry 31:1100–1112
White, S.H., King, G.I. 1985. Molecular packing and area compressibility of lipid bilayers. Proc. Natl. Acad. Sci. USA 82:6532–6536
White, S.H., King, G.I., Cain, J.E. 1981. Location of hexane in lipid bilayers determined by neutron diffraction. Nature 290:161–163
Windrem, D.A., Plachy, W.Z. 1980. The diffusion-solubility of oxygen in lipid bilayers. Biochim. Biophys. Acta 600:655–665
Worcester, D.L., Franks, N.P. 1976. Structural analysis of hydrated egg lecithin and cholesterol bilayers. II. Neutron diffraction. J. Mol. Biol. 100:359–378
Xiang, T.-X. 1993. A computer simulation of free volume distributions and related structural properties in a model lipid bilayer. Biophys. J. 65:1108–1120
Xiang, T.-X., Anderson, B.D. 1994a. Molecular distributions in lipid bilayers and other interphases: A statistical mechanical theory combined with molecular dynamics simulation. Biophys. J. 66:561–573
Xiang, T.-X., Anderson, B.D. 1994b. The relationship between permeant size and permeability in lipid bilayer membranes. J. Membrane Biol 140:111–121
Xiang, T.-X., Anderson, B.D. 1994c. Substituent contributions to the permeability of substituted p-toluic acids in lipid bilayer membranes. J. Pharm. Sci. 83:1511–1518
Xiang, T.-X., Anderson, B.D. 1995a. Development of a combined NMR paramagnetic ion-induced line-broadening/dynamic light scattering method for permeability measurements across lipid bilayer membranes. J. Pharm. Sci. (in press)
Xiang, T.-X., Anderson, B.D. 1995b. Mean molecular potentials in a model lipid bilayer: A molecular dynamics simulation. J. Chem. Phys. (in press)
Xiang, T.-X., Chen, X., Anderson, B.D. 1992. Transport methods for probing the barrier domain of lipid bilayer membranes. Biophys. J. 63:78–88
Author information
Authors and Affiliations
Additional information
This work was supported by grants from Glaxo, INTERx/Merck, and University of Utah Research Committee.
Rights and permissions
About this article
Cite this article
Xiang, TX., Anderson, B.D. Phospholipid surface density determines the partitioning and permeability of acetic acid in DMPC:cholesterol bilayers. J. Membarin Biol. 148, 157–167 (1995). https://doi.org/10.1007/BF00207271
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00207271