Advertisement

European Biophysics Journal

, Volume 47, Issue 2, pp 151–164 | Cite as

Membrane phase transition during heating and cooling: molecular insight into reversible melting

  • Liping Sun
  • Rainer A. BöckmannEmail author
Original Article
  • 334 Downloads

Abstract

With increasing temperature, lipid bilayers undergo a gel-fluid phase transition, which plays an essential role in many physiological phenomena. In the present work, this first-order phase transition was investigated for variable heating and cooling rates for a dipalmitoylphosphatidylcholine (DPPC) lipid bilayer by means of atomistic molecular dynamics simulations. Alternative methods to track the melting temperature \(T_m\) are compared. The resulting \(T_m\) is shown to be independent of the scan rate for small heating rates (0.05–0.3 K/ns) implying reversible melting, and increases for larger heating (0.3–4 K/ns) or cooling rates (2–0.1 K/ns). The reported dependency of the melting temperature on the heating rate is in perfect agreement with a two-state kinetic rate model as suggested previously. Expansion and shrinkage, as well as the dynamics of melting seeds is described. The simulations further exhibit a relative shift between melting seeds in opposing membrane leaflets as predicted from continuum elastic theory.

Keywords

Molecular dynamics DPPC Phase transition Heating/cooling rate Reversible melting Melting seed 

Notes

Acknowledgements

This work was supported by the German Science Foundation (DFG) within the Research Training Group 1962—Dynamic Interactions at Biological Membranes, the SFB1027—Physical Modeling of Non-Equilibrium Processes in Biological Systems, and by a scholarship from the China Scholarship Council (CSC, to LS).

Supplementary material

Supplementary material 1 (MP4 23,763 kb)

Supplementary material 2 (MP4 25,509 kb)

References

  1. Andersen SS, Jackson AD, Heimburg T (2009) Towards a thermodynamic theory of nerve pulse propagation. Prog Neurobiol 88(2):104–113CrossRefPubMedGoogle Scholar
  2. Andreoli TE, Hoffman JF, Fanestil DD, Schultz SG (1980) Membrane physiology. Springer, BerlinCrossRefGoogle Scholar
  3. Armstrong CL, Barrett M, Toppozini L, Kučerka N, Yamani Z, Katsaras J, Fragneto G, Rheinstädter MC (2012) Co-existence of gel and fluid lipid domains in single-component phospholipid membranes. Soft Matter 8(17):4687–4694CrossRefGoogle Scholar
  4. Biltonen RL, Lichtenberg D (1993) The use of differential scanning calorimetry as a tool to characterize liposome preparations. Chem Phys Lipids 64(1):129–142CrossRefGoogle Scholar
  5. Black S, Dixon G (1981) Alternating current calorimetry of dimyristoylphosphatidylcholine multilayers: hysteresis and annealing near the gel to liquid-crystal transition. Biochemistry 20(23):6740–6744CrossRefPubMedGoogle Scholar
  6. Blicher A, Wodzinska K, Fidorra M, Winterhalter M, Heimburg T (2009) The temperature dependence of lipid membrane permeability, its quantized nature, and the influence of anesthetics. Biophys J 96(11):4581–4591CrossRefPubMedPubMedCentralGoogle Scholar
  7. Blume A (1983) Apparent molar heat capacities of phospholipids in aqueous dispersion. Effects of chain length and head group structure. Biochemistry 22(23):5436–5442CrossRefGoogle Scholar
  8. Brooks BR, Bruccoleri RE, Olafson BD, Swaminathan S, Karplus M et al (1983) Charmm: a program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 4(2):187–217CrossRefGoogle Scholar
  9. Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126(1):014,101CrossRefGoogle Scholar
  10. Callen H (1960) Thermodynamics: an introduction to the physical theories of equilibrium thermostatics and irreversible thermodynamics. Wiley, New YorkGoogle Scholar
  11. Cevc G, Richardsen H (1999) Lipid vesicles and membrane fusion. Adv Drug Deliv Rev 38(3):207–232CrossRefPubMedGoogle Scholar
  12. Chapman D (1975) Phase transitions and fluidity characteristics of lipids and cell membranes. Q Rev Biophys 8(02):185–235CrossRefPubMedGoogle Scholar
  13. Chapman D, Byrne P, Shipley G (1966) The physical properties of phospholipids. I. Solid state and mesomorphic properties of some 2, 3-diacyl-dl-phosphatidylethanolamines. Proc R Soc Lond Ser A 290(1420):115–142CrossRefGoogle Scholar
  14. Chapman D, Williams R, Ladbrooke B (1967) Physical studies of phospholipids. VI. Thermotropic and lyotropic mesomorphism of some 1, 2-diacyl-phosphatidylcholines (lecithins). Chem Phys Lipids 1(5):445–475CrossRefGoogle Scholar
  15. Darden T, York D, Pedersen L (1993) Particle mesh Ewald: an N\(\cdot\) log (N) method for Ewald sums in large systems. J Chem Phys 98(10):089Google Scholar
  16. Davies MA, Brauner JW, Schuster HF, Mendelsohn R (1990) A quantitative infrared determination of acyl chain conformation in gramicidin/dipalmitoylphosphatidylcholine mixtures. Biochem Biophys Res Commun 168(1):85–90CrossRefPubMedGoogle Scholar
  17. Davis JH (1979) Deuterium magnetic resonance study of the gel and liquid crystalline phases of dipalmitoyl phosphatidylcholine. Biophys J 27(3):339CrossRefPubMedPubMedCentralGoogle Scholar
  18. Debnath A, Thakkar FM, Maiti PK, Kumaran V, Ayappa K (2014) Laterally structured ripple and square phases with one and two dimensional thickness modulations in a model bilayer system. Soft Matter 10(38):7630–7637CrossRefPubMedGoogle Scholar
  19. Devaux P, McConnell H (1972) Lateral diffusion in spin-labeled phosphatidylcholine multilayers. J Am Chem Soc 94(13):4475–4481CrossRefPubMedGoogle Scholar
  20. de Vries AH, Yefimov S, Mark AE, Marrink SJ (2005) Molecular structure of the lecithin ripple phase. Proc Natl Acad Sci USA 102(15):5392–5396CrossRefPubMedPubMedCentralGoogle Scholar
  21. Dickson CJ, Madej BD, Skjevik AA, Betz RM, Teigen K, Gould IR, Walker RC (2014) Lipid14: the Amber lipid force field. J Chem Theory Comput 10(2):865–879CrossRefPubMedPubMedCentralGoogle Scholar
  22. Fanning DW (2000) IDL programming techniques. Fanning software consulting, Fort CollinsGoogle Scholar
  23. Feller SE, MacKerell AD (2000) An improved empirical potential energy function for molecular simulations of phospholipids. J Phys Chem B 104(31):7510–7515CrossRefGoogle Scholar
  24. Feller SE, Venable RM, Pastor RW (1997) Computer simulation of a DPPC phospholipid bilayer: structural changes as a function of molecular surface area. Langmuir 13(24):6555–6561CrossRefGoogle Scholar
  25. Galimzyanov TR, Molotkovsky RJ, Bozdaganyan ME, Cohen FS, Pohl P, Akimov SA (2012) Elastic membrane deformations govern interleaflet coupling of lipid-ordered domains. Phys Rev Lett 115(8):088,101CrossRefGoogle Scholar
  26. Ginnings D, Furukawa G (1953) Heat capacity standards for the range 14–1200 degrees K.-correction. J Am Chem Soc 75(24):6359–6359CrossRefGoogle Scholar
  27. Heimburg T (2000) A model for the lipid pretransition: coupling of ripple formation with the chain-melting transition. Biophys J 78(3):1154–1165CrossRefPubMedPubMedCentralGoogle Scholar
  28. Heimburg T, Jackson AD (2005) On soliton propagation in biomembranes and nerves. Proc Natl Acad Sci USA 102(28):9790–9795CrossRefPubMedPubMedCentralGoogle Scholar
  29. Henn FA, Thompson TE (1969) Synthetic lipid bilayer membranes. Annu Rev Biochem 38(1):241–262CrossRefPubMedGoogle Scholar
  30. Hess B, Bekker H, Berendsen HJ, Fraaije JG et al (1997) Lincs: a linear constraint solver for molecular simulations. J Comput Chem 18(12):1463–1472CrossRefGoogle Scholar
  31. Hess B, Kutzner C, Van Der Spoel D, Lindahl E (2008) GROMACS 4: algorithms for highly efficient, load-balanced, and scalable molecular simulation. J Chem Theory Comput 4(3):435–447CrossRefPubMedGoogle Scholar
  32. Hurley JH, Boura E, Carlson LA, Różycki B (2010) Membrane budding. Cell 143(6):875–887CrossRefPubMedPubMedCentralGoogle Scholar
  33. Hömberg M, Müller M (2010) Main phase transition in lipid bilayers: phase coexistence and line tension in a soft, solvent-free, coarse-grained model. J Chem Phys 132(155):104Google Scholar
  34. Janiak MJ, Small DM, Shipley GG (1976) Nature of the thermal pretransition of synthetic phospholipids: dimyristoyl- and dipalmitoyllecithin. Biochemistry 15(21):4575–4580CrossRefPubMedGoogle Scholar
  35. Janiak MJ, Small DM, Shipley GG (1979) Temperature and compositional dependence of the structure of hydrated dimyristoyl lecithin. J Biol Chem 254(13):6068–6078PubMedGoogle Scholar
  36. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML (1983) Comparison of simple potential functions for simulating liquid water. J Chem Phys 79(2):926–935CrossRefGoogle Scholar
  37. Jämbeck JPM, Lyubartsev AP (2012) Derivation and systematic validation of a refined all-atom force field for phosphatidylcholine lipids. J Phys Chem B 116(10):3164–3179CrossRefPubMedPubMedCentralGoogle Scholar
  38. Kharakoz D, Colotto A, Lohner K, Laggner P (1993) Fluid-gel interphase line tension and density fluctuations in dipalmitoylphosphatidylcholine multilamellar vesicles: an ultrasonic study. J Phys Chem 97(38):9844–9851CrossRefGoogle Scholar
  39. Kharakoz DP, Shlyapnikova EA (2000) Thermodynamics and kinetics of the early steps of solid-state nucleation in the fluid lipid bilayer. J Phys Chem B 104(44):10368–10378CrossRefGoogle Scholar
  40. Kissinger HE (1957) Reaction kinetics in differential thermal analysis. Anal Chem 29(11):1702–1706CrossRefGoogle Scholar
  41. Klauda JB, Venable RM, Freites JA, OConnor JW, Tobias DJ, Mondragon-Ramirez C, Vorobyov I, MacKerell AD Jr, Pastor RW (2010) Update of the CHARMM all-atom additive force field for lipids: validation on six lipid types. J Phys Chem B 114(23):7830–7843CrossRefPubMedPubMedCentralGoogle Scholar
  42. Kociurzynski R, Pannuzzo M, Böckmann RA (2015) Phase transition of glycolipid membranes studied by coarse-grained simulations. Langmuir 31:9379–9387CrossRefPubMedGoogle Scholar
  43. Kowalik B, Schubert T, Wada H, Tanaka M, Netz RR, Schneck E (2015) Combination of MD simulations with two-state kinetic rate modeling elucidates the chain melting transition of phospholipid bilayers for different hydration levels. J Phys Chem B 119(44):14157–14167CrossRefPubMedGoogle Scholar
  44. Krasikova IN, Khotimchenko SV, Solov’eva TF, Ovodov YS (1995) Mutual influence of plasmid profile and growth temperature on the lipid composition of Yersinia pseudotuberculosis bacteria. Biochim Biophys Acta Lipids Lipid Metab 1257(2):118–124CrossRefGoogle Scholar
  45. Leekumjorn S, Sum AK (2007) Molecular studies of the gel to liquid-crystalline phase transition for fully hydrated DPPC and DPPE bilayers. Biochim Biophys Acta Biomembr 1768(2):354–365CrossRefGoogle Scholar
  46. Leontiadou H, Mark AE, Marrink SJ (2004) Molecular dynamics simulations of hydrophilic pores in lipid bilayers. Biophys J 86(4):2156–2164CrossRefPubMedPubMedCentralGoogle Scholar
  47. Lippert J, Peticolas W (1972) Raman active vibrations in long-chain fatty acids and phospholipid sonicates. Biochim Biophys Acta Biomembr 282:8–17CrossRefGoogle Scholar
  48. Mabrey S, Sturtevant JM (1976) Investigation of phase transitions of lipids and lipid mixtures by sensitivity differential scanning calorimetry. Proc Natl Acad Sci USA 73(11):3862–3866CrossRefPubMedPubMedCentralGoogle Scholar
  49. MacKerell AD, Bashford D, Bellott MLDR, Dunbrack RL, Evanseck JD, Field MJ, Fischer S, Gao J, Guo H, Ha S, Joseph-McCarthy D, Kuchnir L, Kuczera K, Lau FTK, Mattos C, Michnick S, Ngo T, Nguyen DT, Prodhom B, Reiher WE, Roux B, Schlenkrich M, Smith JC, Stote R, Straub J, Watanabe M, Wiórkiewicz-Kuczera J, Yin D, Karplus M (1998) All-atom empirical potential for molecular modeling and dynamics studies of proteins. J Phys Chem B 102(18):3586–3616CrossRefPubMedGoogle Scholar
  50. Marrink SJ, Peter Tieleman D (2002) Molecular dynamics simulation of spontaneous membrane fusion during a cubic-hexagonal phase transition. Biophys J 83(5):2386–2392CrossRefPubMedPubMedCentralGoogle Scholar
  51. Marrink SJ, Risselada J, Mark AE (2005) Simulation of gel phase formation and melting in lipid bilayers using a coarse grained model. Chem Phys Lipids 135(2):223–244CrossRefPubMedGoogle Scholar
  52. Mendelsohn R, Davies M, Brauner J, Schuster H, Dluhy R (1989) Quantitative determination of conformational disorder in the acyl chains of phospholipid bilayers by infrared spectroscopy. Biochemistry 28(22):8934–8939CrossRefPubMedGoogle Scholar
  53. Nagai T, Ueoka R, Okamoto Y (2012) Phase behavior of a lipid bilayer system studied by a replica-exchange molecular dynamics simulation. J Phys Soc Jpn 81(024):002Google Scholar
  54. Nagle JF (1980) Theory of the main lipid bilayer phase transition. Annu Rev Phys Chem 31(1):157–196CrossRefGoogle Scholar
  55. Nagle J (1993) Arealipid of bilayers from NMR. Biophys J 64(5):1476CrossRefPubMedPubMedCentralGoogle Scholar
  56. Nagle J, Scott H (1978) Lateral compressibility of lipid mono-and bilayers. Theory of membrane permeability. Biochim Biophys Acta Biomembr 513(2):236–243CrossRefGoogle Scholar
  57. Neuenfeld S, Schick C (2006) Verifying the symmetry of differential scanning calorimeters concerning heating and cooling using liquid crystal secondary temperature standards. Thermochim Acta 446(1):55–65CrossRefGoogle Scholar
  58. Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52(12):7182–7190CrossRefGoogle Scholar
  59. Picquart M, Lefévre T (2003) Raman and fourier transform infrared study of phytol effects on saturated and unsaturated lipid multibilayers. J Raman Spectrosc 34(1):4–12CrossRefGoogle Scholar
  60. Pluhackova K, Böckmann RA (2015) Biomembranes in atomistic and coarse-grained simulations. J Phys Condens Matter 27(32):323,103CrossRefGoogle Scholar
  61. Pluhackova K, Kirsch SA, Han J, Sun L, Jiang Z, Unruh T, Böckmann RA (2016) A critical comparison of biomembrane force fields: structure and dynamics of model DMPC, POPC, and POPE bilayers. J Phys Chem B 120(16):3888–3903CrossRefPubMedGoogle Scholar
  62. Qin SS, Yu ZW, Yu YX (2009) Structural characterization on the gel to liquid-crystal phase transition of fully hydrated DSPC and DSPE bilayers. J Phys Chem B 113(23):8114–8123CrossRefPubMedGoogle Scholar
  63. Riske KA, Barroso RP, Vequi-Suplicy CC, Germano R, Henriques VB, Lamy MT (2009) Lipid bilayer pre-transition as the beginning of the melting process. Biochim Biophys Acta Biomembr 1788(5):954–963CrossRefGoogle Scholar
  64. Sandoval-Perez A, Pluhackova K, Böckmann RA (2017) Critical comparison of biomembrane force fields: protein-lipid interactions at the membrane interface. J Chem Theory Comput 13:2310–2321CrossRefPubMedGoogle Scholar
  65. Schmitt T, Frezzatti W, Schreier S (1993) Hemin-induced lipid membrane disorder and increased permeability: a molecular model for the mechanism of cell lysis. Arch Biochem Biophys 307(1):96–103CrossRefPubMedGoogle Scholar
  66. Schrödinger LLC (2015) The PyMOL molecular graphics system, version 1.8Google Scholar
  67. Schubert T, Schneck E, Tanaka M (2011) First order melting transitions of highly ordered dipalmitoyl phosphatidylcholine gel phase membranes in molecular dynamics simulations with atomistic detail. J Chem Phys 135(055):105Google Scholar
  68. Siu SWI, Pluhackova K, Böckmann RA (2012) Optimization of the OPLS-AA force field for long hydrocarbons. J Chem Theory Comput 8(4):1459–1470CrossRefPubMedGoogle Scholar
  69. Steim JM, Tourtellotte ME, Reinert JC, McElhaney RN, Rader RL (1969) Calorimetric evidence for the liquid-crystalline state of lipids in a biomembrane. Proc Natl Acad Sci USA 63(1):104–109CrossRefPubMedPubMedCentralGoogle Scholar
  70. Tardieu A, Luzzati V, Reman F (1973) Structure and polymorphism of the hydrocarbon chains of lipids: a study of lecithin-water phases. J Mol Biol 75(4):711–733CrossRefPubMedGoogle Scholar
  71. Tenchov B (1991) On the reversibility of the phase transitions in lipid-water systems. Chem Phys Lipids 57(2):165–177CrossRefPubMedGoogle Scholar
  72. Traeubl H, Sackmann E (1972) Crystalline-liquid crystalline phase transition of lipid model membranes. III. Structure of a steroid-lecithin system below and above the lipid-phase transition. J Am Chem Soc 94(13):4499–4510CrossRefGoogle Scholar
  73. Trudell JR (1977) A unitary theory of anesthesia based on lateral phase separations in nerve membranes. Anesthesiology 46(1):5–10CrossRefPubMedGoogle Scholar
  74. Tsuchida K, Ohki K, Sekiya T, Nozawa Y, Hatta I (1987) Dynamics of appearance and disappearance of the ripple structure in multilamellar liposomes of dipalmitoylphosphatidylcholine. Biochim Biophys Acta Biomembr 898(1):53–58CrossRefGoogle Scholar
  75. Tu K, Tobias DJ, Klein ML (1995) Constant pressure and temperature molecular dynamics simulation of a fully hydrated liquid crystal phase dipalmitoylphosphatidylcholine bilayer. Biophys J 69(6):2558CrossRefPubMedPubMedCentralGoogle Scholar
  76. Vega C, Abascal JL (2011) Simulating water with rigid non-polarizable models: a general perspective. Phys Chem Chem Phys 13(44):19663–19688CrossRefPubMedGoogle Scholar
  77. Wiener M, Suter R, Nagle J (1989) Structure of the fully hydrated gel phase of dipalmitoylphosphatidylcholine. Biophys J 55(2):315–325CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© European Biophysical Societies' Association 2017

Authors and Affiliations

  1. 1.Computational Biology, Department of BiologyFriedrich-Alexander-University of Erlangen-NürnbergErlangenGermany

Personalised recommendations