Life evolution and
atmospheric
oxygen pressure
Cholesterol and its influence
in lipid membranes
Alejandro P. Heuck
Dept. Biochemistry and Molecular Biology
Life- as a Matter of Fat. The emerging Science of Lipidomics.
Ole G. Mouritsen. Springer 2005
Available at: UM Science ; TX545 .M68 2005
Mole %
Biosynthetic pathway for synthesis of
cholesterol
1
16
16
0
0.7
7
0
15
5
Voet Biochemistry 3e Page 394
© 2004 John Wiley & Sons, Inc.
40
Lipid Compositions of Some Biological Membranes
Phospholipids have different acyl chains
Dimensions of the phospholipids molecules
DSPE
Dimensions of the phospholipids
molecules and cholesterol
DSPC
SOPC
Exploring lateral heterogeneity
in synthetic membranes
DSPC
fluid or “liquid”
solid or “gel”
Phase transition and phases in DPPC
Lipid membrane phases
crystalline
Gel
Solid-ordered
ripple
Thermal Biophysics of Membranes
Thomas Heimburg. Wiley-VCH 2007
Available at: UM Science ; QH601 .H44 2007
Liquid disordered
Phase diagram of lipid bilayers of binary
mixtures of PC lipids
DPPC DLPC phase diagram
How does cholesterol affect the
physical properties of lipids bilayers?
Phase diagram of lipid bilayers with
cholesterol
Phase diagrams of lipid mixtures relevant to the study of membrane rafts
BBA 2008 1781, 665-684
Lanosterol is unable to stabilize a
liquid-ordered phase
Ternary phase diagram for
POPC-SM-Cholesterol
Membrane lipids: where they are and how they behave
Nat. Rev. Mol. Cell. Biol.2008. 9, 112-124
Ternary phase diagram
Physical membrane properties
regulated by cholesterol
Cellular cholesterol trafficking and compartmentalization
Nat. Rev. Mol. Cell. Biol.2008. 9, 125-138
• Permeability (ions, glucose, epicholesterol no effect)
• Binding of solutes (EtOH)
• Lateral diffusion (Modest effect, only below Tm)
• Condensing effect (monolayers)
Susceptibility of cholesterol to
cholesterol oxidase on red blood cells
Cholesterol homeostasis and the escape tendency (activity) of plasma membrane cholesterol.
Prog. Lip. Res. 2008, 47, 319-332
Rate of transfer of
dehydrocholesterol to -methyl
cyclodextrin
Perfringolysin O (PFO)
Cholesterol-dependent Cytolysins
• Synthesized and secreted by
Gram-positive bacteria
• Synthesized and secreted as a
water-soluble monomer (53
kDa)
• Bind and oligomerize on
cholesterol-containing
membranes
• Binds to cholesterolcontaining membranes
• Comprised of four different
structural domains
• Forms large transmembrane
pores
Rossjohn et al. 1997
Cell 89, 685
Tilley et al. 2005
Cholesterol Dependence of
Domain 4-membrane Interaction
F/F0
Binding
5
ex = 295 nm
POPC
4
em = 348 nm
3
2
1
25
Protein-lipid Interactions. From Membrane Domains to Cellular Networks.
Edited by Lukas K. Tamm. Wiley-VCH 2005
Available at: UM Science ; QP552.M44 P755 2005
30
35
40
45
50
Mole % cholesterol
55
Heuck et al (2000)
Molec. Cell 6, 1233