Biomedical Engineering Reference
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channel pore whose cross-sectional area changes back-and-forth freely over time.
Unlike transient current transitions in AMP channels, the transition of current in
chemotherapy drug channels is a time-dependent phenomenon. This clearly suggests
that AMP channels undergo structural transitions between distinguishable structures,
e.g., gramicidin's monomer and dimer states (see Fig.
4.2
) and alamethicin's differ-
ent states depending on the participating alamethicin monomers in its barrel-stave
pore, which determine the cylindrical channels' distinguishable cross-sections (see
Figs.
4.3
and
4.4
). Each distinguishable structure represents a discrete current level
in a single AMP channel conductance state. Since all distinguishable structures are
relatively stable, we observe stable amplitudes in all corresponding current levels.
An entirely different current structure is observed in the case of chemotherapy drug
channels. The spontaneous change of current amplitude clearly suggests no specific
structure of the channel with a constant geometrical dimension. Only the broken
membrane model (see the two-dimensional view in Fig.
4.5
) can support the idea
of a time-dependent continuous change of a pore's cross-sectional area. This is a
new effect [
6
,
7
]. The lipidic channels created, for example, by ceramides show
no difference compared to barrel-stave pore type current transitions (for details see
[
3
,
43
,
48
]). However, the current traces which represent defects inside membranes
(see Fig.
4.8
) show another novel behavior. Sudden spikes with apparently no spe-
cific 'amplitude and stability' represent conductance events inside membranes. These
spikes certainly do not provide evidence of an instability of any distinguishable struc-
ture or any specific complex created by the antimicrobial peptide gramicidin S with
lipids. Unlike the certain presence of discrete peaks at specific values of conductance
(representing stable structures of channels) in the point-count-versus-conductance
plots in gramicidin A and alamethicin channels, we observed no discreteness in the
point count plots of the current traces due to both chemotherapy drug channels and
gramicidin S-induced defects.
Based on the analysis of the current traces, we conclude that membrane transport
is characterized by various distinguishable properties of current flows, seen through
the conductance events. Furthermore, the structures of the conductance events show
diverse behavior, depending on the properties of the participating agents and the
membranes.
4.6 General Models for Peptide Pathways and the Creation
of Channels in Membranes
Peptides interacting with lipids in the hydrophobic lipid bilayer environment cre-
ate membrane effects through the creation of various morphological disorders in
membranes. We have so far addressed a few specific cases using a set of AMPs:
gramicidin A, alamethicin, magainin, melittin, colicin, gramicidin S, etc. A spe-
cific peptide is found to create a specific peptide-lipid complex, which means that
active events in membranes are highly specific to the membrane active agents. The
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