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. 1999 Jun;76(6):3176–3185. doi: 10.1016/S0006-3495(99)77469-2

Theoretical analysis of hydrophobic matching and membrane-mediated interactions in lipid bilayers containing gramicidin.

T A Harroun 1, W T Heller 1, T M Weiss 1, L Yang 1, H W Huang 1
PMCID: PMC1300286  PMID: 10354442

Abstract

We present a quantitative analysis of the effects of hydrophobic matching and membrane-mediated protein-protein interactions exhibited by gramicidin embedded in dimyristoylphosphatidylcholine (DMPC) and dilauroylphosphatidylcholine (DLPC) bilayers (Harroun et al., 1999. Biophys. J. 76:937-945). Incorporating gramicidin, at 1:10 peptide/lipid molar ratio, decreases the phosphate-to-phosphate (PtP) peak separation in the DMPC bilayer from 35.3 A without gramicidin to 32.7 A. In contrast, the same molar ratio of gramicidin in DLPC increases the PtP from 30.8 A to 32.1 A. Concurrently, x-ray in-plane scattering showed that the most probable nearest-neighbor separation between gramicidin channels was 26.8 A in DLPC, but reduced to 23.3 A in DMPC. In this paper we review the idea of hydrophobic matching in which the lipid bilayer deforms to match the hydrophobic surface of the embedded proteins. We use a simple elasticity theory, including thickness compression, tension, and splay terms to describe the membrane deformation. The energy of membrane deformation is compared with the energy cost of hydrophobic mismatch. We discuss the boundary conditions between a gramicidin channel and the lipid bilayer. We used a numerical method to solve the problem of membrane deformation profile in the presence of a high density of gramicidin channels and ran computer simulations of 81 gramicidin channels to find the equilibrium distributions of the channels in the plane of the bilayer. The simulations contain four parameters: bilayer thickness compressibility 1/B, bilayer bending rigidity Kc, the channel-bilayer mismatch Do, and the slope of the interface at the lipid-protein boundary s. B, Kc, and Do were experimentally measured; the only free parameter is s. The value of s is determined by the requirement that the theory produces the experimental values of bilayer thinning by gramicidin and the shift in the peak position of the in-plane scattering due to membrane-mediated channel-channel interactions. We show that both hydrophobic matching and membrane-mediated interactions can be understood by the simple elasticity theory.

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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. Arseniev A. S., Barsukov I. L., Bystrov V. F., Lomize A. L., Ovchinnikov YuA 1H-NMR study of gramicidin A transmembrane ion channel. Head-to-head right-handed, single-stranded helices. FEBS Lett. 1985 Jul 8;186(2):168–174. doi: 10.1016/0014-5793(85)80702-x. [DOI] [PubMed] [Google Scholar]
  3. Chothia C. Hydrophobic bonding and accessible surface area in proteins. Nature. 1974 Mar 22;248(446):338–339. doi: 10.1038/248338a0. [DOI] [PubMed] [Google Scholar]
  4. Elliott J. R., Needham D., Dilger J. P., Haydon D. A. The effects of bilayer thickness and tension on gramicidin single-channel lifetime. Biochim Biophys Acta. 1983 Oct 26;735(1):95–103. doi: 10.1016/0005-2736(83)90264-x. [DOI] [PubMed] [Google Scholar]
  5. Evans E, Rawicz W. Entropy-driven tension and bending elasticity in condensed-fluid membranes. Phys Rev Lett. 1990 Apr 23;64(17):2094–2097. doi: 10.1103/PhysRevLett.64.2094. [DOI] [PubMed] [Google Scholar]
  6. 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]
  7. Goulian M., Mesquita O. N., Fygenson D. K., Nielsen C., Andersen O. S., Libchaber A. Gramicidin channel kinetics under tension. Biophys J. 1998 Jan;74(1):328–337. doi: 10.1016/S0006-3495(98)77790-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Harroun T. A., Heller W. T., Weiss T. M., Yang L., Huang H. W. Experimental evidence for hydrophobic matching and membrane-mediated interactions in lipid bilayers containing gramicidin. Biophys J. 1999 Feb;76(2):937–945. doi: 10.1016/S0006-3495(99)77257-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. He K., Ludtke S. J., Worcester D. L., Huang H. W. Neutron scattering in the plane of membranes: structure of alamethicin pores. Biophys J. 1996 Jun;70(6):2659–2666. doi: 10.1016/S0006-3495(96)79835-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. He K., Ludtke S. J., Wu Y., Huang H. W. X-ray scattering with momentum transfer in the plane of membrane. Application to gramicidin organization. Biophys J. 1993 Jan;64(1):157–162. doi: 10.1016/S0006-3495(93)81350-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Hladky S. B., Gruen D. W. Thickness fluctuations in black lipid membranes. Biophys J. 1982 Jun;38(3):251–258. doi: 10.1016/S0006-3495(82)84556-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Ketchem R. R., Hu W., Cross T. A. High-resolution conformation of gramicidin A in a lipid bilayer by solid-state NMR. Science. 1993 Sep 10;261(5127):1457–1460. doi: 10.1126/science.7690158. [DOI] [PubMed] [Google Scholar]
  16. Langs D. A. Three-dimensional structure at 0.86 A of the uncomplexed form of the transmembrane ion channel peptide gramicidin A. Science. 1988 Jul 8;241(4862):188–191. doi: 10.1126/science.2455345. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Mouritsen O. G., Bloom M. Models of lipid-protein interactions in membranes. Annu Rev Biophys Biomol Struct. 1993;22:145–171. doi: 10.1146/annurev.bb.22.060193.001045. [DOI] [PubMed] [Google Scholar]
  19. Méléard P., Gerbeaud C., Pott T., Fernandez-Puente L., Bivas I., Mitov M. D., Dufourcq J., Bothorel P. Bending elasticities of model membranes: influences of temperature and sterol content. Biophys J. 1997 Jun;72(6):2616–2629. doi: 10.1016/S0006-3495(97)78905-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Needham D., Evans E. Structure and mechanical properties of giant lipid (DMPC) vesicle bilayers from 20 degrees C below to 10 degrees C above the liquid crystal-crystalline phase transition at 24 degrees C. Biochemistry. 1988 Oct 18;27(21):8261–8269. doi: 10.1021/bi00421a041. [DOI] [PubMed] [Google Scholar]
  21. Nicholson L. K., Cross T. A. Gramicidin cation channel: an experimental determination of the right-handed helix sense and verification of beta-type hydrogen bonding. Biochemistry. 1989 Nov 28;28(24):9379–9385. doi: 10.1021/bi00450a019. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. Olah G. A., Huang H. W., Liu W. H., Wu Y. L. Location of ion-binding sites in the gramicidin channel by X-ray diffraction. J Mol Biol. 1991 Apr 20;218(4):847–858. doi: 10.1016/0022-2836(91)90272-8. [DOI] [PubMed] [Google Scholar]
  24. Owicki J. C., McConnell H. M. Theory of protein-lipid and protein-protein interactions in bilayer membranes. Proc Natl Acad Sci U S A. 1979 Oct;76(10):4750–4754. doi: 10.1073/pnas.76.10.4750. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Pearson L. T., Edelman J., Chan S. I. Statistical mechanics of lipid membranes. Protein correlation functions and lipid ordering. Biophys J. 1984 May;45(5):863–871. doi: 10.1016/S0006-3495(84)84232-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Wallace B. A., Ravikumar K. The gramicidin pore: crystal structure of a cesium complex. Science. 1988 Jul 8;241(4862):182–187. doi: 10.1126/science.2455344. [DOI] [PubMed] [Google Scholar]
  28. White S. H. Formation of "solvent-free" black lipid bilayer membranes from glyceryl monooleate dispersed in squalene. Biophys J. 1978 Sep;23(3):337–347. doi: 10.1016/S0006-3495(78)85453-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Woolf T. B., Roux B. Structure, energetics, and dynamics of lipid-protein interactions: A molecular dynamics study of the gramicidin A channel in a DMPC bilayer. Proteins. 1996 Jan;24(1):92–114. doi: 10.1002/(SICI)1097-0134(199601)24:1<92::AID-PROT7>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]

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