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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
GROMACS workshopCSC, Espoo, 28 February 2007
Introduction: Lipids
Introduction: SM-SM Interactions
OH-group involved withintramolecular h-bonding
NH-group involved withintermolecular h-bonding
Phosphoryl oxygens involvedwith H20 hydrogen bonding
Niemelä, Hyvönen, Vattulainen (2004) Biophys J, 87:2976 – 2989Niemelä, Hyvönen, Vattulainen (2006) Biophys J, 90:851 – 863
Introduction: CHOL-SM
Aittoniemi, Niemelä, Hyvönen, Karttunen, Vattulainen (2007) Biophys J, 92:1125-1137.
Introduction: Bilayer Phases
Liquiddisordered
Gel Liquid ordered
Traffic, 5 (2004) 241 - 246
Introduction: Domains
http://www.memphys.sdu.dk
http://www.memphys.sdu.dk
Sphingomyelin (SM) + Cholesterol
Phosphatidyl-choline (PC)
de Almeida et al, Biophys. J. 85:2406-2416 (2003)Hancock et al, Nat Rev Mol Cell Biol 7:456-462
< 25 nm
75-100 nm25-75 nm
Introduction: Rafts in Vivo
Schuck et al (2004) J Cell Sci, 117:5955-5964.
Introduction: Rafts in Vivo
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.
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-waterNiemelä, Ollila, Hyvönen, Karttunen, Vattulainen, PLoS Comp Biol (2007) 3:e34.
Equilibration: Area per lipid
Kucerka et al., J. Membr. Biol (2005) 208:193; Hofsäss et al., Biophys. J. (2003) 84:2192
X-ray diffractionPOPC: 0.683 ± 0.015 nm2
MD-simulationDPPC-CHOL 25%0.48 nm2
MD-simulationDPPC-CHOL 40%0.43 nm2
Acyl Chain Ordering
Cn
Cn-1
Cn+1
z
molCD
mol
SS
S
2
1
1cos32
1 2
Lateral DiffusionPOPC:PSM:CHOL DT [10-7 cm2/s]
1:1:1 0.037 ± 0.002
2:1:1 0.08 ± 0.02
62:1:1 0.67 ± 0.06t
tr
dD
tT
)(
2
1lim
2
Filippov et al, Biophys J (2006) 90:2086.
Experiment PFG-NMR: DOPC:PSM:CHOL (10% - 30% CHOL)
DT1 1.0 * 10-7 cm2/sDT2 0.1 * 10-7 cm2/s
Bilayer ThicknessPOPC:PSM:CHOL d [nm]
1:1:1 4.40 ± 0.05
2:1:1 4.29 ± 0.05
62:1:1 3.53 ± 0.05
d = 0.6 nm ... 0.9 nm
Membrane undulations
Lindahl and Edholm., Biophys J, 79 (2000) 426 - 433
)(),( quyxu undund
Undulatory Spectrum
62:1:1
2:1:1
1:1:1
4 qy
Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen, PLoS Comp Biol (2007) 3:e34.
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:CHOL kc [10-20 J] experimental
1:1:1 10 ± 2 120-170% increase, POPC-CHOL (30-50)%2:1:1 7 ± 2
62:1:1 6 ± 2 4 to 9 * 10-20 J
POPC:PSM:CHOL KA [10-3 N/m] experimental
1:1:1 2700 ± 700 1700 (SM:CHOL)
2:1:1 1000 ± 400 780 (PC:CHOL)
62:1:1 200 ± 100 140-300 (PC)
Pressure Profiles
),,(1
)( jiijji
ijislicei
iilocal zzzfmV
z rFvvp
Lindahl et al. , J. Chem. Phys, 113 (2000) 3882-3893
z
0)( dzz
)()()( zPzPz LN
Pressure Profiles
Niemelä, Ollila, Hyvönen, Karttunen, Vattulainen, PLoS Comp Biol (2007) 3:e34.
Lipid-Protein Interactions
R. Cantor, J. Phys. Chem. (1997) 101, 1723-1725
Lipid-Protein Interactionsz
CLOSED
OPEN
Gullingsrud et. al., Biophys J, 86 (2004) 3496-3509
MscL
Lipid-Protein Interactions
dzzAzpW )()(
Mechanical work to create protein-shaped cavity
Work to close one MscL channel in lipid bilayer:
openclosed WWW
Gullingsrud et. al., Biophys J, 86 (2004) 3496-3509
Lipid-Protein Interactions
Work to open MscL in different membrane environments:
POPC:PSM:CHOL W [kBT]
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.
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?
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
Peristaltic Spectrum