Skip to main content
PMC home page
Biophysical Journal logoLink to Biophysical Journal
. 1999 Oct;77(4):2075–2089. doi: 10.1016/S0006-3495(99)77049-9

Structure of dipalmitoylphosphatidylcholine/cholesterol bilayer at low and high cholesterol concentrations: molecular dynamics simulation.

A M Smondyrev 1, M L Berkowitz 1
PMCID: PMC1300489  PMID: 10512828

Abstract

By using molecular dynamics simulation technique we studied the changes occurring in membranes constructed of dipalmitoylphosphatidylcholine (DPPC) and cholesterol at 8:1 and 1:1 ratios. We tested two different initial arrangements of cholesterol molecules for a 1:1 ratio. The main difference between two initial structures is the average number of nearest-neighbor DPPC molecules around the cholesterol molecule. Our simulations were performed at constant temperature (T = 50 degrees C) and pressure (P = 0 atm). Durations of the runs were 2 ns. The structure of the DPPC/cholesterol membrane was characterized by calculating the order parameter profiles for the hydrocarbon chains, atom distributions, average number of gauche defects, and membrane dipole potentials. We found that adding cholesterol to membranes results in a condensing effect: the average area of membrane becomes smaller, hydrocarbon chains of DPPC have higher order, and the probability of gauche defects in DPPC tails is lower. Our results are in agreement with the data available from experiments.

Full Text

The Full Text of this article is available as a PDF (1.4 MB).

Selected References

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

  1. Almeida P. F., Vaz W. L., Thompson T. E. Lateral diffusion in the liquid phases of dimyristoylphosphatidylcholine/cholesterol lipid bilayers: a free volume analysis. Biochemistry. 1992 Jul 28;31(29):6739–6747. doi: 10.1021/bi00144a013. [DOI] [PubMed] [Google Scholar]
  2. Berger O., Edholm O., Jähnig F. Molecular dynamics simulations of a fluid bilayer of dipalmitoylphosphatidylcholine at full hydration, constant pressure, and constant temperature. Biophys J. 1997 May;72(5):2002–2013. doi: 10.1016/S0006-3495(97)78845-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Chong P. L. Evidence for regular distribution of sterols in liquid crystalline phosphatidylcholine bilayers. Proc Natl Acad Sci U S A. 1994 Oct 11;91(21):10069–10073. doi: 10.1073/pnas.91.21.10069. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Douliez J. P., Léonard A., Dufourc E. J. Restatement of order parameters in biomembranes: calculation of C-C bond order parameters from C-D quadrupolar splittings. Biophys J. 1995 May;68(5):1727–1739. doi: 10.1016/S0006-3495(95)80350-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Egberts E., Marrink S. J., Berendsen H. J. Molecular dynamics simulation of a phospholipid membrane. Eur Biophys J. 1994;22(6):423–436. doi: 10.1007/BF00180163. [DOI] [PubMed] [Google Scholar]
  6. Engelman D. M., Rothman J. E. The planar organization of lecithin-cholesterol bilayers. J Biol Chem. 1972 Jun 10;247(11):3694–3697. [PubMed] [Google Scholar]
  7. Hauser H., Pascher I., Pearson R. H., Sundell S. Preferred conformation and molecular packing of phosphatidylethanolamine and phosphatidylcholine. Biochim Biophys Acta. 1981 Jun 16;650(1):21–51. doi: 10.1016/0304-4157(81)90007-1. [DOI] [PubMed] [Google Scholar]
  8. Honig C. R., Reddy Y. S. Calcium, tropomyosin, and actomyosin as controls of calcium binding by troponin. Recent Adv Stud Cardiac Struct Metab. 1975;8:233–240. [PubMed] [Google Scholar]
  9. Hyslop P. A., Morel B., Sauerheber R. D. Organization and interaction of cholesterol and phosphatidylcholine in model bilayer membranes. Biochemistry. 1990 Jan 30;29(4):1025–1038. doi: 10.1021/bi00456a027. [DOI] [PubMed] [Google Scholar]
  10. Ipsen J. H., Mouritsen O. G., Bloom M. Relationships between lipid membrane area, hydrophobic thickness, and acyl-chain orientational order. The effects of cholesterol. Biophys J. 1990 Mar;57(3):405–412. doi: 10.1016/S0006-3495(90)82557-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kintanar A., Kunwar A. C., Oldfield E. Deuterium nuclear magnetic resonance spectroscopic study of the fluorescent probe diphenylhexatriene in model membrane systems. Biochemistry. 1986 Oct 21;25(21):6517–6524. doi: 10.1021/bi00369a027. [DOI] [PubMed] [Google Scholar]
  12. Le Guernevé C., Auger M. New approach to study fast and slow motions in lipid bilayers: application to dimyristoylphosphatidylcholine-cholesterol interactions. Biophys J. 1995 May;68(5):1952–1959. doi: 10.1016/S0006-3495(95)80372-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Marsan M. P., Muller I., Ramos C., Rodriguez F., Dufourc E. J., Czaplicki J., Milon A. Cholesterol orientation and dynamics in dimyristoylphosphatidylcholine bilayers: a solid state deuterium NMR analysis. Biophys J. 1999 Jan;76(1 Pt 1):351–359. doi: 10.1016/S0006-3495(99)77202-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. McIntosh T. J., Magid A. D., Simon S. A. Cholesterol modifies the short-range repulsive interactions between phosphatidylcholine membranes. Biochemistry. 1989 Jan 10;28(1):17–25. doi: 10.1021/bi00427a004. [DOI] [PubMed] [Google Scholar]
  15. McMullen T. P., Lewis R. N., McElhaney R. N. Differential scanning calorimetric study of the effect of cholesterol on the thermotropic phase behavior of a homologous series of linear saturated phosphatidylcholines. Biochemistry. 1993 Jan 19;32(2):516–522. doi: 10.1021/bi00053a016. [DOI] [PubMed] [Google Scholar]
  16. Mendelsohn R., Davies M. A., Schuster H. F., Xu Z. C., Bittman R. CD2 rocking modes as quantitative infrared probes of one-, two-, and three-bond conformational disorder in dipalmitoylphosphatidylcholine and dipalmitoylphosphatidylcholine/cholesterol mixtures. Biochemistry. 1991 Sep 3;30(35):8558–8563. doi: 10.1021/bi00099a010. [DOI] [PubMed] [Google Scholar]
  17. Morrow M. R., Singh D., Lu D., Grant C. W. Glycosphingolipid fatty acid arrangement in phospholipid bilayers: cholesterol effects. Biophys J. 1995 Jan;68(1):179–186. doi: 10.1016/S0006-3495(95)80173-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Oldfield E., Meadows M., Rice D., Jacobs R. Spectroscopic studies of specifically deuterium labeled membrane systems. Nuclear magnetic resonance investigation of the effects of cholesterol in model systems. Biochemistry. 1978 Jul 11;17(14):2727–2740. doi: 10.1021/bi00607a006. [DOI] [PubMed] [Google Scholar]
  19. Pearson R. H., Pascher I. The molecular structure of lecithin dihydrate. Nature. 1979 Oct 11;281(5731):499–501. doi: 10.1038/281499a0. [DOI] [PubMed] [Google Scholar]
  20. Rice D. M., Meadows M. D., Scheinman A. O., Goñi F. M., Gómez-Fernández J. C., Moscarello M. A., Chapman D., Oldfield E. Protein-lipid interactions. A nuclear magnetic resonance study of sarcoplasmic reticulum Ca2,Mg2+-ATPase, lipophilin, and proteolipid apoprotein-lecithin systems and a comparison with the effects of cholesterol. Biochemistry. 1979 Dec 25;18(26):5893–5903. [PubMed] [Google Scholar]
  21. Robinson A. J., Richards W. G., Thomas P. J., Hann M. M. Behavior of cholesterol and its effect on head group and chain conformations in lipid bilayers: a molecular dynamics study. Biophys J. 1995 Jan;68(1):164–170. doi: 10.1016/S0006-3495(95)80171-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sankaram M. B., Thompson T. E. Modulation of phospholipid acyl chain order by cholesterol. A solid-state 2H nuclear magnetic resonance study. Biochemistry. 1990 Nov 27;29(47):10676–10684. doi: 10.1021/bi00499a015. [DOI] [PubMed] [Google Scholar]
  23. Smondyrev A. M., Berkowitz M. L. Molecular dynamics simulation of DPPC bilayer in DMSO. Biophys J. 1999 May;76(5):2472–2478. doi: 10.1016/S0006-3495(99)77402-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tu K., Klein M. L., Tobias D. J. Constant-pressure molecular dynamics investigation of cholesterol effects in a dipalmitoylphosphatidylcholine bilayer. Biophys J. 1998 Nov;75(5):2147–2156. doi: 10.1016/S0006-3495(98)77657-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Tu K., Tobias D. J., Blasie J. K., Klein M. L. Molecular dynamics investigation of the structure of a fully hydrated gel-phase dipalmitoylphosphatidylcholine bilayer. Biophys J. 1996 Feb;70(2):595–608. doi: 10.1016/S0006-3495(96)79623-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Tu K., Tobias D. J., Klein M. L. Constant pressure and temperature molecular dynamics simulation of a fully hydrated liquid crystal phase dipalmitoylphosphatidylcholine bilayer. Biophys J. 1995 Dec;69(6):2558–2562. doi: 10.1016/S0006-3495(95)80126-8. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Urbina J. A., Pekerar S., Le H. B., Patterson J., Montez B., Oldfield E. Molecular order and dynamics of phosphatidylcholine bilayer membranes in the presence of cholesterol, ergosterol and lanosterol: a comparative study using 2H-, 13C- and 31P-NMR spectroscopy. Biochim Biophys Acta. 1995 Sep 13;1238(2):163–176. doi: 10.1016/0005-2736(95)00117-l. [DOI] [PubMed] [Google Scholar]
  28. Vanderkooi G. Computation of mixed phosphatidylcholine-cholesterol bilayer structures by energy minimization. Biophys J. 1994 May;66(5):1457–1468. doi: 10.1016/S0006-3495(94)80936-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Vanderkooi G. Multibilayer structure of dimyristoylphosphatidylcholine dihydrate as determined by energy minimization. Biochemistry. 1991 Nov 5;30(44):10760–10768. doi: 10.1021/bi00108a022. [DOI] [PubMed] [Google Scholar]
  30. Vist M. R., Davis J. H. Phase equilibria of cholesterol/dipalmitoylphosphatidylcholine mixtures: 2H nuclear magnetic resonance and differential scanning calorimetry. Biochemistry. 1990 Jan 16;29(2):451–464. doi: 10.1021/bi00454a021. [DOI] [PubMed] [Google Scholar]
  31. Voglino L., McIntosh T. J., Simon S. A. Modulation of the binding of signal peptides to lipid bilayers by dipoles near the hydrocarbon-water interface. Biochemistry. 1998 Sep 1;37(35):12241–12252. doi: 10.1021/bi9805792. [DOI] [PubMed] [Google Scholar]

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

RESOURCES