The Membrane as a Transporter, Ion Channels and Membrane Pumps - Membrane Biophysics, Biological and Medical Physics, Biomedical Engineering - page 59

the membranes takes some specific forms which are understandable and can be mod-
eled. However, there exist some other ways a few agents can create disorders inside
membranes, in contrast to these ordered structures. These structural disorders, often
referred to as 'defects', may occasionally be compared to events that are responsi-
ble for creating conductive properties in a non-channel fashion inside membranes.
Since they are random disorders, it is hard to schematize them, due to their diverse
appearances. Nonetheless, many attempts have been made by researchers to model
them using scientific analogy. The in-plane diffusion model of Bechinger or similar
models (as in [ 12 , 13 ]) are relevant examples. In the Bechinger model, the insertion
of antimicrobial peptides into phospholipid bilayers is assumed to disorganize the
hydrocarbon chains of adjacent phospholipid molecules, creating a local thinning
of the bilayer and increasing the cross-sectional area per phospholipid molecule.
This process finally leads to local disturbances in bilayer packing, and leads to an
increased bilayer permeability. Such a bilayer perturbation requires minimal pep-
tide aggregation, which would be both entropically and electrically unfavorable. Yet,
these regions of instability may eventually overlap due to lateral diffusion within the
membrane, thereby producing transient “openings” of a variety of sizes. Evidence
of such defects has recently been found by us while investigating the membrane
effects of a small AMP gramicidin S [ 9 ]. This gramicidin S-induced destabilization
of the phospholipid bilayer is expected to be enhanced with the insertion of additional
peptide molecules, and with an increasing trans-membrane potential, as was indeed
observed. Also, the bilayer properties, participating lipids, andhydrocarbons were
all found to play a concomitant role in the induction of the AMP-induced defects
or non-channel conductance events in our study that found a novel mechanism of
action [ 9 ].
4.5 Comparative Analysis of the Electrical Conductance States
that Determine the Membrane's Transport Properties
Induced by Ion Channels or Other Conductance Events
In Fig. 4.7 we have presented our electrophysiology results in terms of current traces
recorded across phospholipid/n-decane membranes doped with channel-forming
antimicrobial peptides or chemotherapy drug molecules as examples of current
traces through ion channels. The AMP-induced channels are found to be transporting
currents with distinguishable amplitudes considering their different conformational
states and rectangular current events in current-versus-time plots which are found
in these cases (see for example both linear β -helical gramicidin A and barrel-stave
alamethicin channel currents). The transitions between different current states are
transient, meaning the transition takes no measurable time. The current traces through
the proposed thiocolchicoside (TCC)- and taxol (TXL)-induced toroidal channels
show no clear constant current amplitudes that might represent any specific conduc-
tance state. We believe that the triangular current events in these cases represent a