Skip to main content
SpringerLink
Log in

Effect of small molecules on the dipalmitoyl lecithin liposomal bilayer: III. Phase transition in lipid bilayer

  • Published:
The Journal of Membrane Biology Aims and scope Submit manuscript

Summary

The effect of more than ninety lipid-soluble compounds on the phase transition behavior ofdl-α-dipalmitoyl lecithin bilayer has been examined by differential scanning calorimetry. The type of effect on the phase transition profile depends on the nature of the additive, whereas the extent of the effect depends on the concentration. The compounds examined include uncouplers, alkanols, fatty acids, detergents, organic solvents, ionophores, inorganic ions, and some commonly used spin-labelled and fluorescent membrane probes. A qualitatively distinct effect of several of these additives on the phase transition behavior of bilayer provides a method of determining the nature of the perturbation they induce in the bilayer organization. The observations are consistent with the hypothesis that the type of effect induced by an additive on the phase transition profile of the bilayer is related to the position of localization of the additive along the thickness of the bilayer. At least four different types of modified transition profiles that are related to changes in bilayer fluidity can be distinguished. These correspond to the localization of the additive in phosphorylcholine (type D), glycerol backbone (type B), C1–C8 methylene (type A), C9–C16 methylene (type C) region of the bilayer. A possible relationship between the type of phase transition profiles of modified liposomes and the physiological effects of drugs is also discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Ahkong, Q.F., Fisher, D., Tampion, W., Lucy, J.A. 1973. The fusion of erythrocytes by fatty acids, esters, retinol and α-tocopherol.Biochem. J. 136:147

    PubMed  Google Scholar 

  • Bieri, V.G., Wallach, D.F.H., Lin, P.S. 1974. Focal erythrocyte membrane perturbations caused by nitroxide lipid analogues.Proc. Nat. Acad. Sci. USA 71:4797

    PubMed  Google Scholar 

  • Brink, F., Posternak, J.M. 1948. Thermodynamic analysis of the relative effectiveness of narcotics.J. Cell. Comp. Physiol. 32:211

    Google Scholar 

  • Broadhurst, M.G. 1963. An analysis of the solid phase behavior of the normal paraffins.J. Res. NBS 66A:241

    Google Scholar 

  • Butler, J.A.V., Ramchandrani, C.N., Thomson, D.W. 1935. The solubility of non-electrolytes. Part I. The free energy of hydration of some aliphatic alcohols.J. Chem. Soc. p. 280

  • Cadenhead, D.A., Muller-Landau, F. 1973. Pure and mixed monomolecular films of 12-nitroxide stearate.Biochim. Biophys. Acta 307:279

    PubMed  Google Scholar 

  • Chen, W.L., Hsia, J.C. 1974. Studies on motional characteristics and distribution of protonated and anionic forms of spin-labeled 2,4-dinitrophenol in phospholipid bilayer membranes.Biochemistry 13:4948

    PubMed  Google Scholar 

  • Cunarro, J., Weiner, M.W. 1975. Mechanism of action of agents which uncouple oxidative phosphorylation: Direct correlation between proton carrying and respiratory-releasing properties using rat liver mitochondria.Biochim. Biophys. Acta 387:234

    PubMed  Google Scholar 

  • Dix, J.A., Diamond, J.M., Kevelson, D. 1974. Translational diffusion coefficient and partition coefficient of a spin-labelled solute in lecithin bilayer membranes.Proc. Nat. Acad. Sci. USA 71:474

    PubMed  Google Scholar 

  • Fourcans, B., Jain, M.K. 1975. Role of phospholipids in transport and enzymic reactions.Adv. Lipid Res. 12:147

    Google Scholar 

  • Freese, E., Sheu, C.W., Galliers, E. 1973. Function of lipophilic acids as microbial food additives.Nature (London) 241:321

    Google Scholar 

  • Galla, H.J., Sackmann, E. 1975. Chemically induced phase separation in mixed vesicles containing phosphatidic acid. An optical study.J. Am. Chem. Soc. 97:4114

    PubMed  Google Scholar 

  • Ginsburg, E., Salomon, D., Sreevalsan, T., Freese, E. 1973. Growth inhibition and morphological changes caused by lipophilic acids in mammalian cells.Proc. Nat. Acad. Sci. USA 70:2457

    PubMed  Google Scholar 

  • Goddard, E.D., Kung, H.C. 1966. Molecular association in pairs of long chain compounds.Soap Chem. Spec. 42:60

    Google Scholar 

  • Hansch, C., Dunn, W.J. 1972. Linear relationships between lipophilic character and biological activity of drugs.J. Pharm. Sci. 61:1

    PubMed  Google Scholar 

  • Hatefi, Y., Hanstein, W.G. 1969. Solubilization of particulate proteins and nonelectrolytes by chaotropic agents.Proc. Nat. Acad. Sci. USA 62:1129

    PubMed  Google Scholar 

  • Haydon, D.A., Taylor, F.H. 1960. Adsorption at the oil-water interface and the calculation of electrical potentials in the aqueous surface. Phase I. Neutral molecules and a simplified treatment for ions.Phil. Trans. 252:225

    Google Scholar 

  • Helenius, A., Simons, K. 1975. Solubilization of membranes by detergents.Biochim. Biophys. Acta 415:29

    PubMed  Google Scholar 

  • Hersh, L.S. 1971. Cellular narcosis and hydrophobic bonding.In: The Chemistry of Biosurfaces. M.L. Hair, editor. Vol. 1, p. 349. Mercel Dekker Inc., New York

    Google Scholar 

  • Herzfeld, S.H., Corrin, M.L., Harkin, W.D. 1950. The effect of alcohols and of alcohols and salts on the critical micelle concentration of dodecylammonium chloride.J. Phys. Chem. 54:271

    Google Scholar 

  • Hill, M.W. 1974. The effect of anesthetic-like molecules on the phase transition in smectic mesophases of dipalmitoyl lecithin. I. The normal alcohol up to C=9 and three inhalation anesthetics.Biochim. Biophys. Acta 356:117

    PubMed  Google Scholar 

  • Hill, M.W. 1975. Partition coefficients of some anesthetic-like molecules between water and smectic mesophases of dipalmitoyl phosphatidylcholine.Chem. Soc. Trans. 3:149

    Google Scholar 

  • Hinz, H.J., Sturtevant, J.M. 1972. Calorimetric studies of dilute aqueous suspensions of bilayers formed from syntheticl-α-lecithins.J. Biol. Chem. 247:6071

    PubMed  Google Scholar 

  • Huang, C.-H. 1976. Roles of carbonyl oxygens at the bilayer interface in phospholipid-sterol interaction.Nature (London) 259:242

    Google Scholar 

  • Hubbell, W.L., McConnell, H.M. 1971. The molecular motion in spin-labeled phospholipids and membranes.J. Am. Chem. Soc. 93:314

    PubMed  Google Scholar 

  • Jacobson, K., Papahadjopoulos, D. 1975. Phase transitions and phase separations in phospholipid membranes induced by changes in temperature, pH, and concentration of bivalent cations.Biochemistry 14:152

    Google Scholar 

  • Jain, M.K. 1972. The Bimolecular Lipid Membrane: A system. Van Nostrand Reinhold Co., New York

    Google Scholar 

  • Jain, M.K. 1975. Role of cholesterol in biomembranes and related systems.Curr. Top. Membr. Trans. 6:1

    Google Scholar 

  • Jain, M.K., Cordes, E.H. 1973. Phospholipase K. Effect ofn-alkanols on the rate of enzymatic hydrolysis of egg phosphatidylcholine.J. Membrane Biol. 14:101

    Google Scholar 

  • Jain, M.K., Toussaint, D.G., Cordes, E.H. 1973. Kinetics of water penetration into unsonicated liposomes: Effects ofn-alkanols and cholesterol.J. Membrane Biol. 14:1

    Google Scholar 

  • Jain, M.K., White, H.B. 1977. Long-range order in biomembrane.Advanc. Lipid Res. 15:1

    Google Scholar 

  • Jain, M.K., Wu, N., Wray, L.V. 1975. Drug induced phase change in bilayer as possible mode of action of lipid soluble drugs.Nature (London) 255:494

    Google Scholar 

  • Jain, M.K., Wu, N., Morgan, T.K., Briggs, M.S., Murray, R.K. 1976. Phase transition in lipid bilayer. II. Influence of adamantane derivatives.Chem. Phys. Lipids 17:71

    PubMed  Google Scholar 

  • Kantor, H.L., Prestegard, J.H. 1975. Fusion of fatty acid containing lecithin vesicles.Biochemistry 14:1790

    PubMed  Google Scholar 

  • Keith, A.D., Sharnoff, M., Cohn, G.E. 1973. A summary and evaluation of spin labels as probes for biological membrane structure.Biochim. Biophys. Acta 300:379

    PubMed  Google Scholar 

  • Kinoshita, K., Ishikawa, H., Shinoda, K. 1958. Solubility of alcohols in water determined by the surface tension measurement.Bull. Chem. Soc. (Jap) 31:1081

    Google Scholar 

  • Kirkpatrick, F.H., Gordesky, S.E., Marinetti, G.V. 1974. Differential solubilization of proteins, phospholipids and cholesterol of erythrocyte membranes by detergents.Biochim. Biophys. Acta 345:154

    PubMed  Google Scholar 

  • Kosower, E.M., Kosower, N.S., Faltin, Z., Diver, A., Saltoun, G., Frensdorf, A. 1974. Membrane mobility agents. A new class of biologically active molecules.Biochim. Biophys. Acta 363:261

    PubMed  Google Scholar 

  • Kosower, N.S., Kosower, E.M., Wegman, P. 1975. Membrane mobility agents. II. Active promoters of cell fusion.Biochim. Biophys. Acta 404:530

    Google Scholar 

  • Krishnan, K.S., Balaram, P. 1975. Perturbation of lipid structures by fluorescent probes.FEBS Lett. 60:419

    PubMed  Google Scholar 

  • Ladbrooke, B.D., Chapman, D. 1969. Thermal analysis of lipids, proteins and biological membranes. A review and summary of some recent studies.Chem. Phys. Lipids 3:304

    PubMed  Google Scholar 

  • Lee, A.G. 1975. Functional properties of biological membranes: A physical-chemical approach.Progr. Biophys. Mol. Biol. 29:3

    Google Scholar 

  • Leo, A., Hansch, C., Elkins, D. 1971. Partition coefficients and their uses.Chem. Rev. 71:525

    Google Scholar 

  • Levine, Y.K. 1973. X-ray diffraction studies of membranes.Progr. Surface Sci. 3:279

    Google Scholar 

  • Lis, L.J., Kauffman, J.W., Shriver, D.F. 1975. Effect of ions on phospholipid layer structure as indicated by Raman spectroscopy.Biochim. Biophys. Acta 406:453

    PubMed  Google Scholar 

  • Maggio, B., Lucy, J.A. 1975. Studies on mixed monolayers of phospholipids and fusogenic lipids.Biochem. J. 149:597

    PubMed  Google Scholar 

  • Malkin, T. 1931. Alternation in properties of long-carbon-chain compounds.Nature (London) 127:126

    Google Scholar 

  • Mnyukh, Yu. V. 1963. Laws of phase transformation in a series of normal paraffins.J. Phys. Chem. Solids 24:631

    Google Scholar 

  • Molyneux, P., Rhodes, C.T., Swarbrick, J. 1965. Thermodynamics of micellization of N-alkylbetaines.Trans. Faraday Soc. 61:1043

    Google Scholar 

  • Nachbar, M.S., Winkler, W.J., Salton, M.R.J. 1972. The effect of aliphatic alcohols upon the dissociation ofMicrococcus lysodeikticus membrane lipids and proteins.Biochim. Biophys. Acta. 274:83

    PubMed  Google Scholar 

  • Ohnishi, S., Ito, T. 1974. Calcium-induced phase separations in phosphatidyl-serine-phosphatidyl-choline membranes.Biochemistry 13:881

    Google Scholar 

  • Paterson, S.J., Butler, K.W., Huang, P., Labelle, J., Smith, I.C.P., Schneider, H. 1972. The effects of alcohols on lipid bilayers: A spin label study.Biochim. Biophys. Acta 266:597

    PubMed  Google Scholar 

  • Phillips, M.C. 1972. The physical state of phospholipids and cholesterol in monolayers, bilayers, and membranes.Prog. Surface Membr. Sci. 5:139

    Google Scholar 

  • Phillips, M.C., Williams, R.M., Chapman, D. 1969. On the nature of hydrocarbon chain motions in lipid liquid crystals.Chem Phys. Lipids 3:234

    Google Scholar 

  • Posner, A.M., Anderson, J.R., Alexander, A.E. 1952. The surface tension and surface potential of aqueous solutions of normal aliphatic alcohols.J. Colloid Sci. 7:625

    Google Scholar 

  • Reynolds, J.A. 1972. Are inorganic cations essential for the stability of biological membranes?Ann. N.Y. Acad. Sci. 195:75

    PubMed  Google Scholar 

  • Rothman, J.E. 1973. The molecular basis of mesomorphic phase transitions in phospholipid systems.J. Theoret. Biol. 38:1

    Google Scholar 

  • Seelig, A., Seelig, J. 1974. The dynamic structure of fatty acyl chains in a phospholipid bilayer measured by deuterium magnetic resonance.Biochemistry 13:4839

    PubMed  Google Scholar 

  • Seeman, P. 1972. The membrane actions of anesthetics and tranquillizers.Pharmacol. Rev. 24:583

    PubMed  Google Scholar 

  • Sessa, G., Freer, J.H., Colacicco, G., Weissmann, G. 1969. Interaction of a lytic polypeptide, mellitin, with lipid membrane systems.J. Biol. Chem. 244:3575

    PubMed  Google Scholar 

  • Shah, D.O., Schulman, J.H. 1965. Binding of metal ions to monolayers of lecithins, plasmalogen, cardiolipin, and dicetylphosphate.J. Lipid Res. 6:341

    Google Scholar 

  • Shah, D.O., Schulman, J.H. 1967. The ionic structure of lecithin monolayers.J. Lipid Res. 8:227

    PubMed  Google Scholar 

  • Sheetz, M.P., Chan, S.I. 1972. Effect of sonication on the structure of lecithin bilayers.Biochemistry 11:4573

    PubMed  Google Scholar 

  • Shimshick, E.J., McConnell, H.M. 1973. Lateral phase separation in phospholipid membranes.Biochemistry 12:2351

    Google Scholar 

  • Simon, S.A., Lis, L.J., Kauffman, J.W., MacDonald, R.C. 1975. A calorimetric and monolayer investigation of the influence of ions on the thermodynamic properties of phosphatidylcholine.Biochim. Biophys. Acta 375:317

    PubMed  Google Scholar 

  • Smith, R., Tanford, C. 1973. Hydrophobicity of long chainn-alkyl carboxylic acids, as measured by their distribution between heptane and aqueous solution.Proc. Nat. Acad. Sci. USA 70:289

    Google Scholar 

  • Stowe, B.B., Dotts, M.A. 1971. The molecular length of effective lipids.Plant Physiol. 48:559

    Google Scholar 

  • Sullivan, K.H., Jain, M.K., Koch, A.L. 1974. Activation of the β-galactoside transport system inEscherichia coli ML-308 byn-alkanols: Modification of lipid-protein interaction by a change in bilayer fluidity.Biochim. Biophys. Acta 352:288

    Google Scholar 

  • Sundaralingam, M., Jensen, L.H. 1965. Crystal and molecular structure of a phospholipid component:l-α-glycerophosphorylcholine cadmium chloride trihydrate.Science 150:1035

    PubMed  Google Scholar 

  • Suurkuusk, J., Lentz, B.R., Barenholz, Y., Biltonen, R.L., Thompson, T.E. 1976. A calorimetric and fluorescent probe study of the gel-liquid crystalline phase transition in small, single-lamellar dipalmitoylphosphatidylcholine vesicles.Biochemistry 15:1393

    PubMed  Google Scholar 

  • Tanford, C. 1972. Hydrophobic free energy, micelle formation and the association of proteins with amphiphiles.J. Mol. Biol. 67:59

    PubMed  Google Scholar 

  • Tinoco, J.D., Ghosh, A.D., Keith, A.D. 1972. Interaction of spin-labelled lipid molecules with natural lipids in monolayers at the air-water interface.Biochim. Biophys. Acta 274:279

    PubMed  Google Scholar 

  • Tomkiewicz, M., Corker, G.A. 1975. Rotational correlation times and partition coefficients of a spin label solute in lecithin vesicles.Biochim. Biophys. Acta 406:197

    PubMed  Google Scholar 

  • Trauble, H. 1971. Phase numwandlungen im lipiden magliche schaltprozesse im biologischen membranes.Naturwissenschaften 58:277

    PubMed  Google Scholar 

  • Trauble, H., Eibl, H. 1974. Electrostatic effects on lipid phase transitions: Membrane structure and ionic environment.Proc. Nat. Acad. Sci. USA 71:214

    PubMed  Google Scholar 

  • Verma, S.P., Wallach, D.F.H., Smith, I.C.P. 1974. The action of mellitin on phosphatide multibilayers as studied by infrared dichroism and spin labeling. A model approach to lipid-protein interactions.Biochim. Biophys. Acta 345:129

    PubMed  Google Scholar 

  • Yemni, T., McCullough, R.L. 1973. Energetics of phase transformations in polyethylene.J. Polymer Sci. 11:1385

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry and Division of Health Sciences, University of Delaware, 19711, Newark, Delaware

    Mahendra Kumar Jain & Nora Min Wu

Authors
  1. Mahendra Kumar Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Nora Min Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jain, M.K., Wu, N.M. Effect of small molecules on the dipalmitoyl lecithin liposomal bilayer: III. Phase transition in lipid bilayer. J. Membrain Biol. 34, 157–201 (1977). https://doi.org/10.1007/BF01870299

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01870299

Keywords

Search

Navigation