The Membrane as a Transporter, Ion Channels and Membrane Pumps - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 65

presence of charge-bearing peptides in the vicinity. For example, the outer monolay-
ers of bacterial plasma membranes are rich in negative phospholipids (which usually
increase the local concentrations of cationic peptides), whereas the membranes of
healthy vertebrate cells appear neutral. Most of the tumor cells lose part of their lipid
asymmetry, and thus exhibit anionic character in their exterior. In addition to these
asymmetries in membrane charge properties, there exists a trans-membrane electric
potential. Large inner-negative trans-membrane potentials are observed in respiring
prokaryotic cells, but not in erythrocytes [ 35 ]. Despite all these electrical properties
due to the composition of the outer leaflet of red cell membranes and the negligi-
ble trans-membrane electric potential, electrostatic contributions are claimed to be
small in the membrane association of peptides [ 14 , 35 ]. Membrane association and
the lytic activities of cationic amphiphiles are claimed to be governed by hydrophobic
interactions with membranes instead. These hydrophobic interactions are functions
of the hydrophobic angle, the hydrophobic moment, and the overall hydrophobicity
of the peptides [ 21 , 54 , 56 ]. To better understand the effects related to membrane
association of peptides, the reader is referred to a very important review [ 13 ] and an
earlier publication [ 12 ] by Bechinger. The lipid membrane's hydrophobic properties
along with local charge properties of both lipids and peptides together determine
the membrane association of peptides. However, once the peptides are already on
or inside the lipid bilayer membrane, the peptide membrane's energetic coupling
determines how the functions of the various peptide-induced membrane transport
events and their biophysical properties are regulated. The energetics of these interac-
tions also determine transitions between different peptide states, such as a monomer
(or free) state and states of various complexes associated with lipids. The flowchart
in Fig. 4.9 shows the region where the energetics discussed above play a role. In the
previous sections, we have discussed the structural complexities of a few of these
different peptide states in membranes, and the consequent antimicrobial activities
due to specific AMPs. Despite this specificity the models of channel formation or
general membrane effects of peptides can be separated into several general classes.
These are briefly explained below.
4.6.1 The Trans-Membrane Helical Bundle Model
A step-wise conductance change (increase or decrease) is often explained using this
model. Figure 4.11 a[ 13 ] is a general representation of this type of model. Alame-
thicin channels (as described in Sect. 4.1.2 ) best represent this trans-membrane helical
bundle model. The addition or subtraction of peptides into or from a cylindrical chan-
nel accounts for the increase or decrease, respectively, of the channel's cross-sectional
area. As a result, the channel conductance experiences a sharp transition between
different current levels. Based on this hypothesis, we have also provided a model
diagram for alamethicin channel structure as presented earlier in Sect. 4.1.2 [ 6 ].