The Membrane as a Transporter, Ion Channels and Membrane Pumps - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 67

In the model diagram presented in Fig. 4.11 b[ 13 ], two monolayers meet each other
through a lipid line where the lipid head groups touch the cylindrical channel. This
model, therefore, represents a type of toroidal structure where both lipids and peptides
align across the toroidal openings [ 31 , 33 ]. Magainin was, for example, found to form
a pore of this type [ 18 ].
4.6.3 The Carpet Model
Figure 4.11 c represents a schematic diagram [ 13 ] of the Carpet model. The model
suggests that as peptides accumulate on the membrane and in the pore, they expe-
rience an approximately 90 ◦ rotation (which is considered to be trans-membrane
orientation) to penetrate into the bilayer. The peptides then participate in creating a
trans-bilayer pore. In this case, the bilayer thickness near the pore is assumed not to
vanish, as is partially shown in the toroidal pore in Fig. 4.10 b. Some peptides with
11-15 leucines or lysines, for example, were found to have high levels of antibiotic
activities [ 14 ], but the peptides with maximal antibiotic activity are too short to cross
the membrane. Therefore, these peptides and other similar ones are observed to be
oriented parallel to the membrane surface [ 17 ]. However, a 34-residue peptide called
dermaseptin, which is rich in lysine and can be configured into an amphipathic
α -helix through residues 1-27, is found to apparently not follow the previously
claimed length-dependent membrane model. Despite having a greater length, it is
found to localize at the membrane surface and then associate in a carpet-like struc-
ture, specifically in the presence of negatively charged lipids in the membrane and
at high peptide concentrations [ 41 ]. This suggests that the model structure followed
by any peptide depends not only on the properties of that specific peptide, but also
to some extent on the membrane constituents.
4.6.4 Detergent-Like Effects
Cationic amphiphiles are most likely to induce considerable cytotoxic activity by
disrupting the bilayer, if not always in a gross manner, perhaps often locally. Any
bilayer disruption causes the loss of bilayer barrier properties, leading to substantial
diffusion of materials across the membrane between inner and outer cellular regions.
This also interferes with the membrane-associated energy metabolism. Detergents
are often found to create this kind of bilayer disruption, which is schematized in
Fig. 4.11 d[ 13 ]. In this detergent-like membrane disruption, it is possible that at the
boundary of the disrupted region the lipids align like a toroidal pore in which the lipid
head groups align across the pore region and the tails point toward the hydrophobic
membrane interior core. To create the detergent-like effects that cause the membrane
disruption (Fig. 4.10 d), a relatively high concentration of detergent (e.g. triton X-100)
or in some cases peptides (e.g. magainin) is needed [ 24 , 45 ].