Skip to main content
NCBI home page
Biophysical Journal logoLink to Biophysical Journal
. 1993 Nov;65(5):1795–1809. doi: 10.1016/S0006-3495(93)81249-9

A molecular model for lipid-protein interaction in membranes: the role of hydrophobic mismatch.

D R Fattal 1, A Ben-Shaul 1
PMCID: PMC1225915  PMID: 8298013

Abstract

The interaction free energy between a hydrophobic, transmembrane, protein and the surrounding lipid environment is calculated based on a microscopic model for lipid organization. The protein is treated as a rigid hydrophobic solute of thickness dP, embedded in a lipid bilayer of unperturbed thickness doL. The lipid chains in the immediate vicinity of the protein are assumed to adjust their length to that of the protein (e.g., they are stretched when dP > doL) in order to bridge over the lipid-protein hydrophobic mismatch (dP-doL). The bilayer's hydrophobic thickness is assumed to decay exponentially to its asymptotic, unperturbed, value. The lipid deformation free energy is represented as a sum of chain (hydrophobic core) and interfacial (head-group region) contributions. The chain contribution is calculated using a detailed molecular theory of chain packing statistics, which allows the calculation of conformational properties and thermodynamic functions (in a mean-field approximation) of the lipid tails. The tails are treated as single chain amphiphiles, modeled using the rotational isometric state scheme. The interfacial free energy is represented by a phenomenological expression, accounting for the opposing effects of head-group repulsions and hydrocarbon-water surface tension. The lipid deformation free energy delta F is calculated as a function of dP-doL. Most calculations are for C14 amphiphiles which, in the absence of a protein, pack at an average area per head-group ao approximately equal to 32 A2 (doL approximately 24.5 A), corresponding to the fluid state of the membrane. When dP = doL, delta F > 0 and is due entirely to the loss of conformational entropy experienced by the chains around the protein. When dP > doL, the interaction free energy is further increased due to the enhanced stretching of the tails. When dP < doL, chain flexibility (entropy) increases, but this contribution to delta F is overcounted by the increase in the interfacial free energy. Thus, delta F obtains a minimum at dP-doL approximately 0. These qualitative interpretations are supported by detailed numerical calculations of the various contributions to the interaction free energy, and of chain conformational properties. The range of the perturbation of lipid order extends typically over few molecular diameters. A rather detailed comparison of our approach to other models is provided in the discussion.

Full text

PDF
1795

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bloom M., Evans E., Mouritsen O. G. Physical properties of the fluid lipid-bilayer component of cell membranes: a perspective. Q Rev Biophys. 1991 Aug;24(3):293–397. doi: 10.1017/s0033583500003735. [DOI] [PubMed] [Google Scholar]
  2. Dill K. A., Naghizadeh J., Marqusee J. A. Chain molecules at high densities at interfaces. Annu Rev Phys Chem. 1988;39:425–461. doi: 10.1146/annurev.pc.39.100188.002233. [DOI] [PubMed] [Google Scholar]
  3. Dill K. A., Stigter D. Lateral interactions among phosphatidylcholine and phosphatidylethanolamine head groups in phospholipid monolayers and bilayers. Biochemistry. 1988 May 3;27(9):3446–3453. doi: 10.1021/bi00409a048. [DOI] [PubMed] [Google Scholar]
  4. Edholm O., Johansson J. Lipid bilayer polypeptide interactions studied by molecular dynamics simulation. Eur Biophys J. 1987;14(4):203–209. doi: 10.1007/BF00256353. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. 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]
  8. 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]
  9. Jähnig F. Critical effects from lipid-protein interaction in membranes. I. Theoretical description. Biophys J. 1981 Nov;36(2):329–345. doi: 10.1016/S0006-3495(81)84735-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jähnig F., Vogel H., Best L. Unifying description of the effect of membrane proteins on lipid order. Verification for the melittin/dimyristoylphosphatidylcholine system. Biochemistry. 1982 Dec 21;21(26):6790–6798. doi: 10.1021/bi00269a027. [DOI] [PubMed] [Google Scholar]
  11. Kurrle A., Rieber P., Sackmann E. Reconstitution of transferrin receptor in mixed lipid vesicles. An example of the role of elastic and electrostatic forces for protein/lipid assembly. Biochemistry. 1990 Sep 11;29(36):8274–8282. doi: 10.1021/bi00488a011. [DOI] [PubMed] [Google Scholar]
  12. Lewis B. A., Engelman D. M. Lipid bilayer thickness varies linearly with acyl chain length in fluid phosphatidylcholine vesicles. J Mol Biol. 1983 May 15;166(2):211–217. doi: 10.1016/s0022-2836(83)80007-2. [DOI] [PubMed] [Google Scholar]
  13. 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]
  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. 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]
  16. Nagle J. F., Wiener M. C. Structure of fully hydrated bilayer dispersions. Biochim Biophys Acta. 1988 Jul 7;942(1):1–10. doi: 10.1016/0005-2736(88)90268-4. [DOI] [PubMed] [Google Scholar]
  17. Nagle J. F., Wilkinson D. A. Lecithin bilayers. Density measurement and molecular interactions. Biophys J. 1978 Aug;23(2):159–175. doi: 10.1016/S0006-3495(78)85441-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Nezil F. A., Bloom M. Combined influence of cholesterol and synthetic amphiphillic peptides upon bilayer thickness in model membranes. Biophys J. 1992 May;61(5):1176–1183. doi: 10.1016/S0006-3495(92)81926-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Owicki J. C., Springgate M. W., McConnell H. M. Theoretical study of protein--lipid interactions in bilayer membranes. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1616–1619. doi: 10.1073/pnas.75.4.1616. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Pearson L. T., Chan S. I., Lewis B. A., Engelman D. M. Pair distribution functions of bacteriorhodopsin and rhodopsin in model bilayers. Biophys J. 1983 Aug;43(2):167–174. doi: 10.1016/S0006-3495(83)84337-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Pink D. A., Chapman D. Protein-lipid interactions in bilayer membranes: a lattice model. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1542–1546. doi: 10.1073/pnas.76.4.1542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Riegler J., Möhwald H. Elastic interactions of photosynthetic reaction center proteins affecting phase transitions and protein distributions. Biophys J. 1986 Jun;49(6):1111–1118. doi: 10.1016/S0006-3495(86)83740-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ring A. Influence of ion occupancy and membrane deformation on gramicidin A channel stability in lipid membranes. Biophys J. 1992 May;61(5):1306–1315. doi: 10.1016/S0006-3495(92)81939-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Scott H. L., Cherng S. L. Monte Carlo studies of phospholipid lamellae: effects of proteins, cholesterol, bilayer curvature, and lateral mobility on order parameters. Biochim Biophys Acta. 1978 Jul 4;510(2):209–215. doi: 10.1016/0005-2736(78)90021-4. [DOI] [PubMed] [Google Scholar]
  26. Scott H. L., Jr, Coe T. J. A theoretical study of lipid-protein interactions in bilayers. Biophys J. 1983 Jun;42(3):219–224. doi: 10.1016/S0006-3495(83)84389-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Seelig J., Seelig A. Lipid conformation in model membranes and biological membranes. Q Rev Biophys. 1980 Feb;13(1):19–61. doi: 10.1017/s0033583500000305. [DOI] [PubMed] [Google Scholar]
  28. Sperotto M. M., Mouritsen O. G. Mean-field and Monte Carlo simulation studies of the lateral distribution of proteins in membranes. Eur Biophys J. 1991;19(4):157–168. doi: 10.1007/BF00196342. [DOI] [PubMed] [Google Scholar]
  29. Wiener M. C., White S. H. Structure of a fluid dioleoylphosphatidylcholine bilayer determined by joint refinement of x-ray and neutron diffraction data. II. Distribution and packing of terminal methyl groups. Biophys J. 1992 Feb;61(2):428–433. doi: 10.1016/S0006-3495(92)81848-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Wilkinson D. A., Nagle J. F. Dilatometry and calorimetry of saturated phosphatidylethanolamine dispersions. Biochemistry. 1981 Jan 6;20(1):187–192. doi: 10.1021/bi00504a031. [DOI] [PubMed] [Google Scholar]
  31. Zhang Y. P., Lewis R. N., Hodges R. S., McElhaney R. N. Interaction of a peptide model of a hydrophobic transmembrane alpha-helical segment of a membrane protein with phosphatidylcholine bilayers: differential scanning calorimetric and FTIR spectroscopic studies. Biochemistry. 1992 Nov 24;31(46):11579–11588. doi: 10.1021/bi00161a042. [DOI] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES