Abstract:
Gramicidin is an antibiotic peptide that can be incorporated into the monolayers of
cell membranes. Dimerization through hydrogen bonding between gramicidin monomers
in opposing leaflets of the membrane results in the formation of an iontophoretic channel.
Surrounding phospholipids, with various associated mechanical properties, have been
shown to influence the gating properties of this channel. Conversely, gramicidin
incorporation has been shown to affect the structure of spontaneously formed lipid
assemblies. Using small-angle x-ray diffraction and model systems composed of
phospholipids and gramicidin, the physical effects incurred by gramicidin incorporation
were measured.
The reverse hexagonal (H^) phase composed of dioleoylphosphatidylethanolamine
(DOPE) monolayers decreased in lattice dimension with increasing incorporation of
gramicidin. This indicated that gramicidin was adding negative curvature to the
monolayers. In this system, gramicidin was measured to have an apparent intrinsic radius
of curvature (Rop*™") of -7. 1 A. The addition of up to 4 mol% gramicidin in mixtures with
DOPE did not result in the monolayers becoming stiffer, as indicated by unaltered bending
moduli for each composition.
Dioleoylphosphatidylcholine (DOPC) alone forms the lamellar (LJ phase when
hydrated, but undergoes a transition into the H^ phase when mixed with gramicidin. The
lattice repeat dimension decreases systematically with increased gramicidin content. Again,
this indicated that gramicidin was adding negative curvature to the monolayers. At 12
mol% gramicidin in mixtures with DOPC, the apparent radius of intrinsic curvature of
gramicidin (Rop*"^) was measured to be -7.4 A. This mixture formed monolayers that were
very resistant to bending under osmotic pressure, with a measured bending modulus of 1 15
kT.
The measurements made in this study demonstrate that peptides are able to modulate
the spontaneous curvature and other mechanical properties of phospholipid assemblies.
