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Assessing the Nature of Lipid Raft Membranes Perttu Niemelä Laboratory of Physics and Helsinki Institute of Physics, Helsinki University of Technology.

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Presentation on theme: "Assessing the Nature of Lipid Raft Membranes Perttu Niemelä Laboratory of Physics and Helsinki Institute of Physics, Helsinki University of Technology."— Presentation transcript:

1 Assessing the Nature of Lipid Raft Membranes Perttu Niemelä Laboratory of Physics and Helsinki Institute of Physics, Helsinki University of Technology GROMACS workshop CSC, Espoo, 28 February 2007

2 Introduction: Lipids

3 Introduction: SM-SM Interactions OH-group involved with intramolecular h-bonding NH-group involved with intermolecular h-bonding Phosphoryl oxygens involved with H 2 0 hydrogen bonding Niemelä, Hyvönen, Vattulainen (2004) Biophys J, 87:2976 – 2989 Niemelä, Hyvönen, Vattulainen (2006) Biophys J, 90:851 – 863

4 Introduction: CHOL-SM Aittoniemi, Niemelä, Hyvönen, Karttunen, Vattulainen (2007) Biophys J, 92:

5 Introduction: Bilayer Phases Liquid disordered GelLiquid ordered Traffic, 5 (2004)

6 Introduction: Domains Sphingomyelin (SM) + Cholesterol Phosphatidyl- choline (PC) de Almeida et al, Biophys. J. 85: (2003) Hancock et al, Nat Rev Mol Cell Biol 7: < 25 nm nm nm

7 Introduction: Rafts in Vivo Schuck et al (2004) J Cell Sci, 117:

8 Introduction: Rafts in Vivo

9 Lipid Mixtures POPC:SM:CHOL 1:1:1 POPC:SM:CHOL 2:1:1 POPC:SM:CHOL 62:1:1 Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen, PLoS Comp Biol (2007) 3:e34.

10 Simulation Details: 1024 lipids / system ~ 30 waters/lipid time-step 2 fs simulation length ns T = 310 K (Nose-Hoover) p = 1 atm (Parrinello-R.)  = 0 (P N = P L ) periodic boundaries Lipids: Force fields previously validated OPLS/Berger-97 (lipid.itp) + GROMOS United atoms for CH2/CH3 Explicit hydrogens for NH/OH SPC-water Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen, PLoS Comp Biol (2007) 3:e34.

11 Equilibration: Area per lipid Kucerka et al., J. Membr. Biol (2005) 208:193; Hofsäss et al., Biophys. J. (2003) 84:2192 X-ray diffraction POPC: ± nm 2 MD-simulation DPPC-CHOL 25% 0.48 nm 2 MD-simulation DPPC-CHOL 40% 0.43 nm 2

12 Acyl Chain Ordering CnCn C n-1 C n+1 z

13 Lateral Diffusion POPC:PSM:CHOL D T [10 -7 cm 2 /s] 1:1: ± :1:10.08 ± :1:10.67 ± 0.06 Filippov et al, Biophys J (2006) 90:2086. Experiment PFG-NMR: DOPC:PSM:CHOL (10% - 30% CHOL) D T1  1.0 * cm 2 /s D T2  0.1 * cm 2 /s

14 Bilayer Thickness POPC:PSM:CHOLd [nm] 1:1:14.40 ± :1:14.29 ± :1:13.53 ± 0.05  d = 0.6 nm nm

15 Membrane undulations Lindahl and Edholm., Biophys J, 79 (2000)

16 Undulatory Spectrum 62:1:1 2:1:1 1:1:1 Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen, PLoS Comp Biol (2007) 3:e34.

17 Elastic Properties Rawicz et al (2000) Biophys J. 79:328; Evans et al. (1990) PRL 64:2094; Needham et al (1990) 58:997; Henriksen et al (2004) Eur Biophys J 33:732 POPC:PSM:CHOLk c [ J]experimental 1:1:110 ± % increase, POPC-CHOL (30-50)% 2:1:17 ± 2 62:1:16 ± 24 to 9 * J POPC:PSM:CHOLK A [10 -3 N/m]experimental 1:1:12700 ± (SM:CHOL) 2:1:11000 ± (PC:CHOL) 62:1:1200 ± (PC)

18 Pressure Profiles Lindahl et al., J. Chem. Phys, 113 (2000) z

19 Pressure Profiles Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen, PLoS Comp Biol (2007) 3:e34.

20 Lipid-Protein Interactions R. Cantor, J. Phys. Chem. (1997) 101,

21 Lipid-Protein Interactions z CLOSED OPEN Gullingsrud et. al., Biophys J, 86 (2004) MscL

22 Lipid-Protein Interactions Mechanical work to create protein-shaped cavity Work to close one MscL channel in lipid bilayer: Gullingsrud et. al., Biophys J, 86 (2004)

23 Lipid-Protein Interactions Work to open MscL in different membrane environments: POPC:PSM:CHOL  W [k B T] 1:1:1 11  2 2:1:1 4  1 1:0:0 1.9  0.2 0:1:0 1.0  0.6 1:0:1 (DPPC) 1.0  0.4 Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen, PLoS Comp Biol (2007) 3:e34.

24 Summary Increased SM and CHOL concentration leads to ordered, rigid and slow bilayers Pressure profiles in raft and non-raft mixtures differ -> effects on proteins?

25 Acknowledgements Other people involved: BIO-group at COMP, Helsinki Univ. of Tech. Academy of Finland CSC, the Finnish IT center for science SDU supercluster (Odense, Denmark) Ilpo Vattulainen Mikko Karttunen Jussi Aittoniemi Marja Hyvönen Samuli Ollila

26 Peristaltic Spectrum


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