Biology Reference
In-Depth Information
including methanol, ethanol
[78]
, and glycerol and some anesthetics including chlorproma-
zine, tetracaine, and benzyl alcohol. The perturbants must be amphipathic and localize at the
aqueous interface where they replace bound waters and increase the effective size of the lipid
head groups. One of the earliest interdigitation experiments involved DSC measurements of
glycerol on DPPC bilayers. In the presence of glycerol (and later other alcohols), the T
m
of
DPPC was initially observed to decrease until a temperature was reached whereupon addi-
tional glycerol resulted in an increase in T
m
. This change in T
m
was referred to as the 'biphasic
effect' and is characteristic of a shift from a noninterdigitated to a fully interdigitated state.
The 'biphasic effect' works better for longer chain PCs but is not observed for PEs.
Also observed with DSC of fully interdigitated state bilayers are hysteresis of heating and
cooling scans and a shift to lower temperature and disappearance of the pre-transition.
Unfortunately, the requirement of pure phospholipids and unrealistically high alcohol
levels (often greater than 1M!), seriously question any biological role for alcohol-induced
interdigitation.
Other perturbants include chaotropic agents (e.g. thiocyanate at 1M), tris buffer, myelin
basic protein, and polymyxin with anionic lipids and increased pressure. Also it must be
noted that ether-linked phospholipids often prefer interdigitation when compared to analo-
gous ester-linked phospholipids. For example, in the gel state, DPPC is noninterdigitated
while DHPC (hexadecyl ether linked-PC) spontaneously interdigitates.
Biological Relevance
While it is clear that a vast array of conditions can drive the normal noninterdigitated state
to several types of interdigitated states, it is not clear whether these transformations are
merely esoteric curiosities or whether they can have some biological relevance. Suggested
biological functions for interdigitation include:
1. Creation of novel membrane micro-domains.
2. Trans-membrane coupling between opposing membrane leaflets.
3. Reduction in charge density per unit area of a membrane surface.
4. Varying membrane thickness, thus altering the hydrophobic match.
SUMMARY
All membrane lipids exhibit different affinities and aversions for one another. An example
of this is the strong affinity of cholesterol for sphingolipids that stabilizes lipid rafts.
Cholesterol-rich lipid mixtures produce a liquid ordered phase whose properties are midway
between gel and liquid crystalline. Cholesterol
>
e
lipid affinity follows the sequence: SM
PS,
>
>
PG
PE and is stronger with saturated than polyunsaturated acyl chains. In addition to
the conventional lipid bilayer (more correctly the lamellar phase), dozens of other phases,
whose functions are unknown, exist. Various lipid mixtures prefer different phases and
complex phase diagrams have been developed that pictorially describe various lipid phases
and can take a wide variety of forms. For an integral protein to achieve maximal activity, the
length of its trans-membrane hydrophobic surface must match the hydrophobic length of the
surrounding bilayer. The Hydrophobic Match is involved in membrane protein activity
and trafficking. Lipids that normally exhibit substantial differences in their acyl chain
PC
