Assessing the Nature of Lipid Raft Membranes

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

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Introduction Lipids
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Introduction SM-SM Interactions
Niemelä, Hyvönen, Vattulainen (2004) Biophys J,
872976 2989 Niemelä, Hyvönen, Vattulainen
(2006) Biophys J, 90851 863
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Introduction CHOL-SM
Aittoniemi, Niemelä, Hyvönen, Karttunen,
Vattulainen (2007) Biophys J, 921125-1137.
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Introduction Bilayer Phases
Traffic, 5 (2004) 241 - 246
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Introduction Domains
Sphingomyelin (SM) Cholesterol
Phosphatidyl- choline (PC)
de Almeida et al, Biophys. J.
852406-2416 (2003) Hancock et al, Nat Rev Mol
Cell Biol 7456-462
http//www.memphys.sdu.dk
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Introduction Rafts in Vivo
Schuck et al (2004) J Cell Sci, 1175955-5964.
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Introduction Rafts in Vivo
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Lipid Mixtures
Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen,
PLoS Comp Biol (2007) 3e34.
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• Simulation Details
• 1024 lipids / system
• 30 waters/lipid
• time-step 2 fs
• simulation length 50-100 ns
• T 310 K (Nose-Hoover)
• p 1 atm (Parrinello-R.)
• ? 0 (PN PL)
• 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) 3e34.
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Equilibration Area per lipid
Kucerka et al., J. Membr. Biol (2005) 208193
Hofsäss et al., Biophys. J. (2003) 842192
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Acyl Chain Ordering
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Lateral Diffusion
POPCPSMCHOL DT 10-7 cm2/s
111 0.037 0.002
211 0.08 0.02
6211 0.67 0.06
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Bilayer Thickness
POPCPSMCHOL d nm
111 4.40 0.05
211 4.29 0.05
6211 3.53 0.05
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Membrane undulations
Lindahl and Edholm., Biophys J, 79 (2000) 426 -
433
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Undulatory Spectrum
6211
211
111
Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen,
PLoS Comp Biol (2007) 3e34.
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Elastic Properties
POPCPSMCHOL kc 10-20 J experimental
111 10 2 120-170 increase, POPC-CHOL (30-50)
211 7 2 120-170 increase, POPC-CHOL (30-50)
6211 6 2 4 to 9 10-20 J
POPCPSMCHOL KA 10-3 N/m experimental
111 2700 700 1700 (SMCHOL)
211 1000 400 780 (PCCHOL)
6211 200 100 140-300 (PC)
Rawicz et al (2000) Biophys J. 79328 Evans et
al. (1990) PRL 642094 Needham et al (1990)
58997 Henriksen et al (2004) Eur Biophys J
33732
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Pressure Profiles
z
Lindahl et al. , J. Chem. Phys, 113 (2000)
3882-3893
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Pressure Profiles
Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen,
PLoS Comp Biol (2007) 3e34.
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Lipid-Protein Interactions
R. Cantor, J. Phys. Chem. (1997) 101, 1723-1725
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Lipid-Protein Interactions
z
MscL
Gullingsrud et. al., Biophys J, 86 (2004)
3496-3509
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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)
3496-3509
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Lipid-Protein Interactions
Work to open MscL in different membrane
environments
POPCPSMCHOL DW kBT
111 11 ? 2
211 4 ? 1
100 1.9 ? 0.2
010 1.0 ? 0.6
101 (DPPC) 1.0 ? 0.4
Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen,
PLoS Comp Biol (2007) 3e34.
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Summary

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

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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)

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Peristaltic Spectrum