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. 1999 Feb;76(2):751–767. doi: 10.1016/S0006-3495(99)77241-3

Molecular theory of lipid-protein interaction and the Lalpha-HII transition.

S May 1, A Ben-Shaul 1
PMCID: PMC1300079  PMID: 9929479

Abstract

We present a molecular-level theory for lipid-protein interaction and apply it to the study of lipid-mediated interactions between proteins and the protein-induced transition from the planar bilayer (Lalpha) to the inverse-hexagonal (HII) phase. The proteins are treated as rigid, membrane-spanning, hydrophobic inclusions of different size and shape, e.g., "cylinder-like," "barrel-like," or "vase-like." We assume strong hydrophobic coupling between the protein and its neighbor lipids. This means that, if necessary, the flexible lipid chains surrounding the protein will stretch, compress, and/or tilt to bridge the hydrophobic thickness mismatch between the protein and the unperturbed bilayer. The system free energy is expressed as an integral over local molecular contributions, the latter accounting for interheadgroup repulsion, hydrocarbon-water surface energy, and chain stretching-tilting effects. We show that the molecular interaction constants are intimately related to familiar elastic (continuum) characteristics of the membrane, such as the bending rigidity and spontaneous curvature, as well as to the less familiar tilt modulus. The equilibrium configuration of the membrane is determined by minimizing the free energy functional, subject to boundary conditions dictated by the size, shape, and spatial distribution of inclusions. A similar procedure is used to calculate the free energy and structure of peptide-free and peptide-rich hexagonal phases. Two degrees of freedom are involved in the variational minimization procedure: the local length and local tilt angle of the lipid chains. The inclusion of chain tilt is particularly important for studying noncylindrical (for instance, barrel-like) inclusions and analyzing the structure of the HII lipid phase; e.g., we find that chain tilt relaxation implies strong faceting of the lipid monolayers in the hexagonal phase. Consistent with experiment, we find that only short peptides (large negative mismatch) can induce the Lalpha --> HII transition. At the transition, a peptide-poor Lalpha phase coexists with a peptide-rich HII phase.

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Selected References

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  1. Aranda-Espinoza H., Berman A., Dan N., Pincus P., Safran S. Interaction between inclusions embedded in membranes. Biophys J. 1996 Aug;71(2):648–656. doi: 10.1016/S0006-3495(96)79265-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Dumas F., Sperotto M. M., Lebrun M. C., Tocanne J. F., Mouritsen O. G. Molecular sorting of lipids by bacteriorhodopsin in dilauroylphosphatidylcholine/distearoylphosphatidylcholine lipid bilayers. Biophys J. 1997 Oct;73(4):1940–1953. doi: 10.1016/S0006-3495(97)78225-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Fattal D. R., Ben-Shaul A. A molecular model for lipid-protein interaction in membranes: the role of hydrophobic mismatch. Biophys J. 1993 Nov;65(5):1795–1809. doi: 10.1016/S0006-3495(93)81249-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Helfrich P., Jakobsson E. Calculation of deformation energies and conformations in lipid membranes containing gramicidin channels. Biophys J. 1990 May;57(5):1075–1084. doi: 10.1016/S0006-3495(90)82625-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Helfrich W. Elastic properties of lipid bilayers: theory and possible experiments. Z Naturforsch C. 1973 Nov-Dec;28(11):693–703. doi: 10.1515/znc-1973-11-1209. [DOI] [PubMed] [Google Scholar]
  6. Huang H. W. Deformation free energy of bilayer membrane and its effect on gramicidin channel lifetime. Biophys J. 1986 Dec;50(6):1061–1070. doi: 10.1016/S0006-3495(86)83550-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Killian J. A. Gramicidin and gramicidin-lipid interactions. Biochim Biophys Acta. 1992 Dec 11;1113(3-4):391–425. doi: 10.1016/0304-4157(92)90008-x. [DOI] [PubMed] [Google Scholar]
  8. Killian J. A., Salemink I., de Planque M. R., Lindblom G., Koeppe R. E., 2nd, Greathouse D. V. Induction of nonbilayer structures in diacylphosphatidylcholine model membranes by transmembrane alpha-helical peptides: importance of hydrophobic mismatch and proposed role of tryptophans. Biochemistry. 1996 Jan 23;35(3):1037–1045. doi: 10.1021/bi9519258. [DOI] [PubMed] [Google Scholar]
  9. Killian J. A., de Kruijff B. Proposed Mechanism for H(II) Phase Induction by Gramicidin in Model Membranes and Its Relation to Channel Formation. Biophys J. 1988 Jan;53(1):111–117. doi: 10.1016/s0006-3495(88)83072-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lewis B. A., Engelman D. M. Bacteriorhodopsin remains dispersed in fluid phospholipid bilayers over a wide range of bilayer thicknesses. J Mol Biol. 1983 May 15;166(2):203–210. doi: 10.1016/s0022-2836(83)80006-0. [DOI] [PubMed] [Google Scholar]
  11. Marcelja S. Lipid-mediated protein interaction in membranes. Biochim Biophys Acta. 1976 Nov 11;455(1):1–7. doi: 10.1016/0005-2736(76)90149-8. [DOI] [PubMed] [Google Scholar]
  12. Marsh D. Lipid-protein interactions and heterogeneous lipid distribution in membranes. Mol Membr Biol. 1995 Jan-Mar;12(1):59–64. doi: 10.3109/09687689509038496. [DOI] [PubMed] [Google Scholar]
  13. Morein S., Strandberg E., Killian J. A., Persson S., Arvidson G., Koeppe R. E., 2nd, Lindblom G. Influence of membrane-spanning alpha-helical peptides on the phase behavior of the dioleoylphosphatidylcholine/water system. Biophys J. 1997 Dec;73(6):3078–3088. doi: 10.1016/S0006-3495(97)78335-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mouritsen O. G., Bloom M. Mattress model of lipid-protein interactions in membranes. Biophys J. 1984 Aug;46(2):141–153. doi: 10.1016/S0006-3495(84)84007-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Nielsen C., Goulian M., Andersen O. S. Energetics of inclusion-induced bilayer deformations. Biophys J. 1998 Apr;74(4):1966–1983. doi: 10.1016/S0006-3495(98)77904-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Piknová B., Pérochon E., Tocanne J. F. Hydrophobic mismatch and long-range protein/lipid interactions in bacteriorhodopsin/phosphatidylcholine vesicles. Eur J Biochem. 1993 Dec 1;218(2):385–396. doi: 10.1111/j.1432-1033.1993.tb18388.x. [DOI] [PubMed] [Google Scholar]
  17. Ren J., Lew S., Wang Z., London E. Transmembrane orientation of hydrophobic alpha-helices is regulated both by the relationship of helix length to bilayer thickness and by the cholesterol concentration. Biochemistry. 1997 Aug 19;36(33):10213–10220. doi: 10.1021/bi9709295. [DOI] [PubMed] [Google Scholar]
  18. Ryba N. J., Marsh D. Protein rotational diffusion and lipid/protein interactions in recombinants of bovine rhodopsin with saturated diacylphosphatidylcholines of different chain lengths studied by conventional and saturation-transfer electron spin resonance. Biochemistry. 1992 Aug 25;31(33):7511–7518. doi: 10.1021/bi00148a011. [DOI] [PubMed] [Google Scholar]
  19. Seddon J. M. Structure of the inverted hexagonal (HII) phase, and non-lamellar phase transitions of lipids. Biochim Biophys Acta. 1990 Feb 28;1031(1):1–69. doi: 10.1016/0304-4157(90)90002-t. [DOI] [PubMed] [Google Scholar]
  20. Shen L., Bassolino D., Stouch T. Transmembrane helix structure, dynamics, and interactions: multi-nanosecond molecular dynamics simulations. Biophys J. 1997 Jul;73(1):3–20. doi: 10.1016/S0006-3495(97)78042-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Siegel D. P., Epand R. M. The mechanism of lamellar-to-inverted hexagonal phase transitions in phosphatidylethanolamine: implications for membrane fusion mechanisms. Biophys J. 1997 Dec;73(6):3089–3111. doi: 10.1016/S0006-3495(97)78336-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Turner D. C., Gruner S. M. X-ray diffraction reconstruction of the inverted hexagonal (HII) phase in lipid-water systems. Biochemistry. 1992 Feb 11;31(5):1340–1355. doi: 10.1021/bi00120a009. [DOI] [PubMed] [Google Scholar]

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