Biology Reference
In-Depth Information
The most studied example of membrane condensation is with phospholipids and choles-
terol
[14]
. For decades cholesterol has been known to condense fluid state membranes, thus
decreasing their permeability, fluidity, packing free volume, and increasing membrane thick-
ness
[15
e
17]
. However, when cholesterol is added to gel state bilayers, membrane packing is
decreased while permeability, fluidity, and packing free volume are increased. Bilayer thick-
ness is also decreased. It has been proposed that cholesterol-induced condensation, which is
extremely high for sphingolipids and di-saturated phosphatidylcholines, may even be
responsible for the formation and stability of lipid rafts (see Chapter 8). Cholesterol associ-
ates best with acyl chains that have no double bonds before position
9. In contrast,
cholesterol avoids close association with chains that have double bonds before position
6
6
9 (e.g.
g
-linolenic, arachidonic, eicosapentaenoic, and docosahexaenoic acids). In the
normal biological motif where the sn-1 chain is saturated and the sn-2 chain unsaturated,
cholesterol renders area condensation measurements relatively insensitive to structural
changes in the sn-2 chain. Therefore it has been proposed that cholesterol likely orients adja-
cent to the saturated, sn-1 side of a phospholipid.
s
L1
The surface elasticity moduli, C
s
1
, has been proposed to provide a more accurate assess-
ment of cholesterol
e
phospholipid interactions than condensation
[18]
.
C
1
S
¼ð
1
AÞð
Surface Elasticity Moduli,
C
A
p
d
p=
d
Note that C
s
1
is a change in surface pressure with area and so, unlike condensation, is
dynamic.
Smaby et al. (1997)
[18]
used the in-plane elasticity moduli (inverse of the lateral compress-
ibility moduli) to address the question of cholesterol interaction with mixed acyl chain PCs.
The PCs had a saturated sn-1 chain and an sn-2 chain composed of either 14:0, 18:1, 18:2, 20:4
or 22:6. At biological lateral pressure (
30 mN/m) they reported that cholesterol caused the
in-plane elasticity of all of the mixed monolayers to decrease. PCs with more double bonds,
however, were less affected by cholesterol and so these PC/sterol mixtures maintain rela-
tively high in-plane elasticity. For di-saturated PCs the decrease in interfacial elasticity is
~6 to 7 fold with equimolar cholesterol, while with di-polyunsaturated PCs the decrease is
only ~1.7 fold. The unsaturated sn-2 acyl chain strongly modulates the elasticity of the
mixed-chain PC films due to the poor association of the rigid
a
-surface of the sterol ring
with the unsaturated sn-2 chains. These surface pressure measurements on lipid monolayers
indicate that cholesterol will preferentially associate with saturated versus unsaturated acyl
chains. This conclusion is in agreement with results derived from a variety of other method-
ologies (see Chapter 10, section A. Complex Lipid Interactions). Also, it can be concluded that
cholesterol will associate more strongly with the saturated sn-1 chain of a mixed acyl chain
phospholipid, particularly when the sn-2 chain is polyunsaturated.
Lipid 'Squeeze Out'
In some lipid mixtures increasing lateral pressure may force a membrane component to be
excluded or 'squeezed out' of the monolayer
[19]
. An example of this behavior is shown in
