Lipids in Membranes - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 43

three-dimensional non-lamellar lipid phases [ 23 ]. Other structurally different peptide
antibiotics are known to be involved in similar activities. For example, the linear pep-
tides, such as gramicidins A, B, and C [ 12 , 13 , 30 ] and alamethicin [ 11 ], also induce
non-lamellar phase formation when incorporated into appropriate lipid dispersions.
It is, therefore, suggestive that membrane disruption mediated by localized increases
in the membrane monolayer curvature stress could be a general mode of action of
many antimicrobial peptides. Other studies (see [ 33 ] and references therein) suggest
that lipid-peptide interactions are sensitive to relatively small alterations in the chem-
ical structure and physical properties of both the peptide and the host lipid bilayer.
In many cases, the subtlety and complexity of these interactions are not readily
predicted or rationalized by current theoretical models. However, it is also true that
if we can find the mechanisms by which the peptides alter membrane properties, then
we would be able in most cases to draw the picture of energetics (see Eq. 3.3 ) and, as
a result, perhaps also identify the near-correct phospholipid organizations or phases
in the membrane environment. This will be attempted in the next few chapters.
We now discuss some experimentally observed phenomena [ 1 ] which offer
an insight into the antimicrobial peptide-induced modulation of the lipid phase
properties. Peptides alamethicin (Alm), gramicidin S (GS) and Ac-K 2 -

( ) 12 -

LA

) 12 ) are used to study the thermotropic phases in dielaidoylphos-
phatidylethanolamine (DEPE) dispersions. In addition to understanding the effects
of independent peptides, measuring the effects of their binary mixtures reveals
some important lipid phase properties. These projects were designed by Md
Ashrafuzzaman in collaboration with Dr. Ronald McElhaney.
Figure 3.8 shows DSC heating scans of DEPE dispersions containing alamethicin.
Only raw scans showing alamethicin effects are presented here; alamethicin-free
scans are identical to previous reports [ 23 ]. We observe pronounced gel/liquid-
crystalline ( L

(

K 2 -amide ( LA

/ L ) and lamellar/reverse hexagonal ( L / H II ) phase transitions at

β α α

37.6 ◦ C) and T H ( 63.6 ◦ C), respectively. On cooling, L

temperatures T m ( / H II

shows hysteresis (lower T H )but T m shows negligible reduction [ 23 ]. The enthalpies
(

∼ ∼

α

H )atthe L / L and L / H II transitions are 8 . 9 ± 0 . 3 and 0 . 64 ± 0 . 05kcal/mol,

β α α

respectively [ 29 ].
AMPs generally change the co-operativity and energetic strength of both the
L β / L α H )

values for the L β / L α and L α / H II transitions decrease with increasing AMP levels;
about a 50% reduction was observed for 1mole% Alm, and a 30% reduction was
observed for 2.72mole%GS (scans are not shown here). T m decreases onlymodestly,
although the AMPs affects T H dramatically. The effects of an AMP are greatly
altered if said AMP co-exists along with another AMP. For example, the effects of
Alm change significantly if there is a binary presence of GS in the lipid dispersion.
As an example, Fig. 3.9 illustrates the DSC scans showing the effects of a binary
Alm/GS presence in DEPE dispersions. The most important effects are observed in
the transition temperature T H .
Figure 3.10 shows that at low AMP/lipid mole ratios (between 0 and 0.2%) and a
GS-lipid ratio between 0 and 0.136%, T H decreases considerably. When GS is at a
lower concentration (

and L α / H II transition phases (see, for example, Fig. 3.8 ). Enthalpy (

∼ 50%), there is a relatively greater decrease in T H compared