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

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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.

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References

  • Andersen SS, Jackson AD, Heimburg T (2009) Towards a thermodynamic theory of nerve pulse propagation. Prog Neurobiol 88(2):104–113

    Article  PubMed  Google Scholar 

  • Andreoli TE, Hoffman JF, Fanestil DD, Schultz SG (1980) Membrane physiology. Springer, Berlin

    Book  Google Scholar 

  • 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):4687–4694

    Article  Google Scholar 

  • Biltonen RL, Lichtenberg D (1993) The use of differential scanning calorimetry as a tool to characterize liposome preparations. Chem Phys Lipids 64(1):129–142

    Article  CAS  Google Scholar 

  • Black S, Dixon G (1981) Alternating current calorimetry of dimyristoylphosphatidylcholine multilayers: hysteresis and annealing near the gel to liquid-crystal transition. Biochemistry 20(23):6740–6744

    Article  CAS  PubMed  Google Scholar 

  • 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):4581–4591

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Blume A (1983) Apparent molar heat capacities of phospholipids in aqueous dispersion. Effects of chain length and head group structure. Biochemistry 22(23):5436–5442

    Article  CAS  Google Scholar 

  • 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):187–217

    Article  CAS  Google Scholar 

  • Bussi G, Donadio D, Parrinello M (2007) Canonical sampling through velocity rescaling. J Chem Phys 126(1):014,101

    Article  Google Scholar 

  • Callen H (1960) Thermodynamics: an introduction to the physical theories of equilibrium thermostatics and irreversible thermodynamics. Wiley, New York

    Google Scholar 

  • Cevc G, Richardsen H (1999) Lipid vesicles and membrane fusion. Adv Drug Deliv Rev 38(3):207–232

    Article  CAS  PubMed  Google Scholar 

  • Chapman D (1975) Phase transitions and fluidity characteristics of lipids and cell membranes. Q Rev Biophys 8(02):185–235

    Article  CAS  PubMed  Google Scholar 

  • 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):115–142

    Article  CAS  Google Scholar 

  • 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):445–475

    Article  CAS  Google Scholar 

  • 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):089

    Google Scholar 

  • 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):85–90

    Article  CAS  PubMed  Google Scholar 

  • Davis JH (1979) Deuterium magnetic resonance study of the gel and liquid crystalline phases of dipalmitoyl phosphatidylcholine. Biophys J 27(3):339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):7630–7637

    Article  CAS  PubMed  Google Scholar 

  • Devaux P, McConnell H (1972) Lateral diffusion in spin-labeled phosphatidylcholine multilayers. J Am Chem Soc 94(13):4475–4481

    Article  CAS  PubMed  Google Scholar 

  • de Vries AH, Yefimov S, Mark AE, Marrink SJ (2005) Molecular structure of the lecithin ripple phase. Proc Natl Acad Sci USA 102(15):5392–5396

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):865–879

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fanning DW (2000) IDL programming techniques. Fanning software consulting, Fort Collins

    Google Scholar 

  • Feller SE, MacKerell AD (2000) An improved empirical potential energy function for molecular simulations of phospholipids. J Phys Chem B 104(31):7510–7515

    Article  CAS  Google Scholar 

  • 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):6555–6561

    Article  CAS  Google Scholar 

  • 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):088,101

    Article  Google Scholar 

  • Ginnings D, Furukawa G (1953) Heat capacity standards for the range 14–1200 degrees K.-correction. J Am Chem Soc 75(24):6359–6359

    Article  Google Scholar 

  • Heimburg T (2000) A model for the lipid pretransition: coupling of ripple formation with the chain-melting transition. Biophys J 78(3):1154–1165

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Heimburg T, Jackson AD (2005) On soliton propagation in biomembranes and nerves. Proc Natl Acad Sci USA 102(28):9790–9795

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henn FA, Thompson TE (1969) Synthetic lipid bilayer membranes. Annu Rev Biochem 38(1):241–262

    Article  CAS  PubMed  Google Scholar 

  • Hess B, Bekker H, Berendsen HJ, Fraaije JG et al (1997) Lincs: a linear constraint solver for molecular simulations. J Comput Chem 18(12):1463–1472

    Article  CAS  Google Scholar 

  • 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):435–447

    Article  CAS  PubMed  Google Scholar 

  • Hurley JH, Boura E, Carlson LA, Różycki B (2010) Membrane budding. Cell 143(6):875–887

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):104

    Google Scholar 

  • Janiak MJ, Small DM, Shipley GG (1976) Nature of the thermal pretransition of synthetic phospholipids: dimyristoyl- and dipalmitoyllecithin. Biochemistry 15(21):4575–4580

    Article  CAS  PubMed  Google Scholar 

  • Janiak MJ, Small DM, Shipley GG (1979) Temperature and compositional dependence of the structure of hydrated dimyristoyl lecithin. J Biol Chem 254(13):6068–6078

    CAS  PubMed  Google Scholar 

  • 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):926–935

    Article  CAS  Google Scholar 

  • 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):3164–3179

    Article  PubMed  PubMed Central  Google Scholar 

  • 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):9844–9851

    Article  CAS  Google Scholar 

  • 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):10368–10378

    Article  CAS  Google Scholar 

  • Kissinger HE (1957) Reaction kinetics in differential thermal analysis. Anal Chem 29(11):1702–1706

    Article  CAS  Google Scholar 

  • 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):7830–7843

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kociurzynski R, Pannuzzo M, Böckmann RA (2015) Phase transition of glycolipid membranes studied by coarse-grained simulations. Langmuir 31:9379–9387

    Article  CAS  PubMed  Google Scholar 

  • 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):14157–14167

    Article  CAS  PubMed  Google Scholar 

  • 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):118–124

    Article  Google Scholar 

  • 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):354–365

    Article  CAS  Google Scholar 

  • Leontiadou H, Mark AE, Marrink SJ (2004) Molecular dynamics simulations of hydrophilic pores in lipid bilayers. Biophys J 86(4):2156–2164

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lippert J, Peticolas W (1972) Raman active vibrations in long-chain fatty acids and phospholipid sonicates. Biochim Biophys Acta Biomembr 282:8–17

    Article  CAS  Google Scholar 

  • 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):3862–3866

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):3586–3616

    Article  CAS  PubMed  Google Scholar 

  • Marrink SJ, Peter Tieleman D (2002) Molecular dynamics simulation of spontaneous membrane fusion during a cubic-hexagonal phase transition. Biophys J 83(5):2386–2392

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):223–244

    Article  CAS  PubMed  Google Scholar 

  • 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):8934–8939

    Article  CAS  PubMed  Google Scholar 

  • 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):002

    Google Scholar 

  • Nagle JF (1980) Theory of the main lipid bilayer phase transition. Annu Rev Phys Chem 31(1):157–196

    Article  CAS  Google Scholar 

  • Nagle J (1993) Arealipid of bilayers from NMR. Biophys J 64(5):1476

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagle J, Scott H (1978) Lateral compressibility of lipid mono-and bilayers. Theory of membrane permeability. Biochim Biophys Acta Biomembr 513(2):236–243

    Article  CAS  Google Scholar 

  • 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):55–65

    Article  CAS  Google Scholar 

  • Parrinello M, Rahman A (1981) Polymorphic transitions in single crystals: a new molecular dynamics method. J Appl Phys 52(12):7182–7190

    Article  CAS  Google Scholar 

  • 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):4–12

    Article  CAS  Google Scholar 

  • Pluhackova K, Böckmann RA (2015) Biomembranes in atomistic and coarse-grained simulations. J Phys Condens Matter 27(32):323,103

    Article  Google Scholar 

  • 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):3888–3903

    Article  CAS  PubMed  Google Scholar 

  • 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):8114–8123

    Article  CAS  PubMed  Google Scholar 

  • 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):954–963

    Article  CAS  Google Scholar 

  • 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 13:2310–2321

    Article  CAS  PubMed  Google Scholar 

  • 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):96–103

    Article  CAS  PubMed  Google Scholar 

  • Schrödinger LLC (2015) The PyMOL molecular graphics system, version 1.8

  • 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):105

    Google Scholar 

  • Siu SWI, Pluhackova K, Böckmann RA (2012) Optimization of the OPLS-AA force field for long hydrocarbons. J Chem Theory Comput 8(4):1459–1470

    Article  CAS  PubMed  Google Scholar 

  • 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):104–109

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • 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):711–733

    Article  CAS  PubMed  Google Scholar 

  • Tenchov B (1991) On the reversibility of the phase transitions in lipid-water systems. Chem Phys Lipids 57(2):165–177

    Article  CAS  PubMed  Google Scholar 

  • 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):4499–4510

    Article  CAS  Google Scholar 

  • Trudell JR (1977) A unitary theory of anesthesia based on lateral phase separations in nerve membranes. Anesthesiology 46(1):5–10

    Article  CAS  PubMed  Google Scholar 

  • 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):53–58

    Article  CAS  Google Scholar 

  • 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):2558

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Vega C, Abascal JL (2011) Simulating water with rigid non-polarizable models: a general perspective. Phys Chem Chem Phys 13(44):19663–19688

    Article  CAS  PubMed  Google Scholar 

  • Wiener M, Suter R, Nagle J (1989) Structure of the fully hydrated gel phase of dipalmitoylphosphatidylcholine. Biophys J 55(2):315–325

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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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).

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  1. Computational Biology, Department of Biology, Friedrich-Alexander-University of Erlangen-Nürnberg, Staudtstrasse 5, Erlangen, 91058, Germany

    Liping Sun & Rainer A. Böckmann

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Correspondence to Rainer A. Böckmann.

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Sun, L., Böckmann, R.A. Membrane phase transition during heating and cooling: molecular insight into reversible melting. Eur Biophys J 47, 151–164 (2018). https://doi.org/10.1007/s00249-017-1237-3

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