The Membrane as a Transporter, Ion Channels and Membrane Pumps - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 63

peptides: water soluble

(relative hydrophobic/hydrophilic properties)

membrane surface accessible

membrane surface associated

bilayer inserted

Energetics

monomer state
(free peptide state)

pore/channel openings
(peptide lipid complexes)

Fig. 4.9 Peptide pathway flowchart addresses how peptide insertion into membrane (peptide path-
way) ends up creating membrane effects. The membrane action of any peptide mainly depends on
the following two factors: (i) the relative hydrophobic/hydrophilic properties of any peptide deter-
mining the relative probability of insertion into the membrane, (ii) energetics between peptides
and a lipid bilayer in the hydrophobic membrane environment that determines the stability of any
peptide-lipid complex. An in-depth analysis of the energetics of these processes can be found in
Chap. 5

orientations. Figure 4.10 shows how the orientations of the peptide helix axis emerge
using NMR spectra studies on peptides interacting with membranes. During the
membrane insertion, the structures of peptides may change dramatically. This can
be a complete transition of structures from a random coil to a highly helical (e.g.
α -helix) arrangement, or an orientation, rotation, and any other specific type of struc-
tural distortion, etc. A detailed analysis, based on a number of studies, is summarized
in [ 12 ].
As the peptides approach or enter the lipid membrane region, the electrostatic
and hydrophobic interactions of the peptides with the lipid bilayer appear to strongly
regulate the peptides' membrane association properties, and a subsequent potentially
lethal effect on the cell. The surface charge density of lipid bilayers, the localized
charges in lipids (especially in the head group regions), etc., have a huge effect on the
membrane association of cationic peptides. The peptides' own identical charges also
repel each other, which might also affect their membrane association coefficients.
The distribution of charges associated with the lipids in membranes is also membrane
specific. Moreover, as the peptides approach lipid head group regions, the presence
of charges, brought onto the peptides, causes polarization in the localized charge con-
formations in lipid head groups. This is a very simple electrostatic effect. About three
decades ago, Seelig et al. [ 46 ] reported their experimental investigations, which indi-
cated that the phospholipid head groups are sensitive to electric charges and dipole