Teague WE, Fuller NL, Rand RP, Gawrisch
K. Polyunsaturated lipids in
membrane fusion events. Cell Mol Biol Lett 2002;7(2):262-4.
Quantum mechanical (QM) calculations of the torsional energy surface for rotation about vinyl-methylene bonds reveal low barriers to rotation, indicating
an intrinsic propensity toward flexibility.
A 16 ns molecular dynamics (MD) simulation of a
1-stearoyl-2-docosahexaenoyl-sn-glyerco-3-phosphocholine (SDPC) lipid bilayer gave results in good agreement with experimental
data, suggesting an unusually high degree of conformational flexibility of
polyunsaturated hydrocarbon chains in membranes. The complete force field is
included as Supporting Information and is available from
http://www.pharmacy.umaryland.edu/faculty/amackere/research.html. Feller SE, Gawrisch
K, MacKerell AD Jr.
Polyunsaturated fatty acids in lipid bilayers:
intrinsic and environmental contributions to their unique physical properties.
J Am Chem Soc 2002 Jan 16;124(2):318-26.
This review describes (from both the
animal and human literature) the biological consequences of losses in nervous
system docosahexaenoate (DHA) and biological
mechanisms for changes in brain and retinal function. DHA-phospholipids
regulate G-protein (e.g., rhodopsin) signaling that
responds to the degree of unsaturation of the
membrane lipids. DHA protects in a cell
culture model of apoptosis as it increases cellular phosphatidylserine
(PS); also, the loss of DHA leads to a loss in PS. Thus, through its effects on
PS, DHA may regulate cell signaling and cell proliferation. Finally, progress
has been made recently in nuclear delineating differences in molecular
structure and order in biomembranes due to subtle
changes in the degree of phospholipid unsaturation.
Ca(2+)
association constants of polyunsaturated membranes were approximately one-half
those of monounsaturated membranes. Furthermore, strength of Ca(2+)
binding to monounsaturated membranes increased with the addition of
cholesterol, while binding to polyunsaturated lipids was unaffected. The data
suggest that the lipid phosphate groups of phosphatidylcholine
(PC), phosphatidylethanolamine (PE), and phosphatidylserine (PS) in PC/PE/PS (4:4:1, mol/mol) are
primary targets for Ca(2+). Negatively charged serine
in PS controls Ca (2+) binding by lowering the electric surface potential and
elevating cation concentration at the membrane/water
interface. The influence of hydrocarbon chain unsaturation
on Ca(2+) binding is secondary compared to membrane PS
content. Order parameter analysis of individual lipids in the mixture revealed
that Ca(2+) ions did not trigger lateral phase
separation of lipid species as long as all lipids remained liquid-crystalline.
However, depending on temperature and hydrocarbon chain unsaturation,
the lipid with the highest chain melting temperature converted to the gel
state, as observed for the monounsaturated phosphatidylethanolamine
(PE) in PC/PE/PS (4:4:1, mol/mol) at 25 degrees C. Biophys J 2000 Jun;78(6):3011-8 Strength of Ca(2+) binding to retinal lipid
membranes: consequences for lipid organization.
Huster D, Arnold K, Gawrisch K.
Preferential interaction between
cholesterol and polyunsaturated 18:0-22:6 PC, followed by 18:0-22:6 PE and
18:0-22:6 PS, was confirmed by 1H MAS NOESY cross-relaxation rate
differences. Cholesterol preferentially
associates with saturated chains in mixed-chain lipids reflected by higher
saturated chain-to-cholesterol cross-relaxation rates. We propose that
cholesterol forms PC-enriched microdomains in the
polyunsaturated 18:0-22:6 PC/18:0-22:6 PE/18:0-22:6 PS/cholesterol membranes in
which the saturated sn-1 chains are preferentially oriented toward the
cholesterol molecules. Huster D, Arnold K, Gawrisch K. Influence of docosahexaenoic
acid and cholesterol on lateral lipid organization in phospholipid
mixtures. Biochemistry 1998 Dec 8;37(49):17299-308 Mitchell
DC, Gawrisch K, Litman BJ,
The significant increase in water
permeation for membranes with polyunsaturated hydrocarbon chains correlates
with looser packing of polyunsaturated lipids at the lipid-water interface and
the suggested deeper penetration of water into these bilayers.
Ethanol may block water diffusion pathways by occupying points of water entry
into bilayers at the interface. Addition of dioleoylphosphatidylethanolamine
increases lipid packing density and, consequently, reduces permeation rates. Huster D, Jin AJ, Arnold
K, Gawrisch K. Water permeability of polyunsaturated lipid membranes measured by
17O NMR. Biophys J 1997 Aug;73(2):855-864.
Unsaturation lowers chain order, mostly in the lower third of the
hydrocarbon chains. By contrast, the increase in chain order caused by the DOPE
matrix and the decrease in order with increasing temperature have a constant
magnitude for the upper two-thirds of the chain and are smaller for the lower
third. Addition of 2 M ethanol reduced order parameters, in effect reversing
the increase in chain order caused by the DOPE matrix.
Separovic F, Gawrisch
K. Effect of unsaturation on the chain order of phosphatidylcholines
in a dioleoylphosphatidylethanolamine matrix. Biophys J
1996 Jul;71(1):274-282.
Increasing sn-2 chain unsaturation from one to six double bonds resulted in a
1.6-kHz decrease in quadrupolar splittings
of the sn-1 chain in the upper half of the chain (or plateau region) and
maximum splitting difference of 4.4 kHz at methylene
carbon 14. The change in chain order corresponds to a decrease in the 18:0
chain length of 0.4 +/- 0.2 A with 18:2 omega 6 versus 18:1 omega 9 in position
sn-2. Fatty acids containing three or more double bonds in sn-2 showed a
decrease in sn-1 chain length of 0.7 +/- 0.2 A compared with 18:1 omega 9. The
chain length of all lipids decreased with increasing temperature. Holte LL, Peter SA, Sinnwell TM, Gawrisch K.
2H nuclear magnetic resonance order parameter profiles suggest a change
of molecular shape for phosphatidylcholines
containing a polyunsaturated acyl chain. Biophys J
1995 Jun;68(6):2396-2403.