Biomedical Engineering Reference
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of (11 ± 2) pS ( Fig. 10 A ). The observed conductivities for the dif-
ferent alkali cations are in good agreement with the selectivity se-
ries of gramicidin, which is known to be Cs + > K + > Li + .
( b ) Alamethicin
Full functionality of a membrane system is only given if the
lateral mobility of the components is proven. Gramicidin can be
observed in a functional state even in a solid supported membrane
system, in which one leaflet is attached to the substrate as demon-
strated by Cornell and coworkers. 54,55 In contrast, one alamethicin
helix, a peptaibol from Trichoderma viridae , spans the entire lipid
bilayer and forms voltage gated ion channels with multiple con-
ductance levels. This behaviour can be explained by the formation
of transmembrane aggregates according to the barrel stave mecha-
nism. 56 The uptake and release of alamethicin helical monomers
from a channel aggregate accounts for the observed multi-state
conductance levels. 57 The formation of such helix bundles requires
the lateral movement of the individual helices. We analyzed
whether such helix bundles are formed, if alamethicin is reconsti-
tuted into nano-BLMs. The nano-BLMs were bathed in 500 mM
KCl and alamethicin was added only to the cis side from an etha-
nolic solution, resulting in a final concentration of about 100 nM,
while applying a holding potential of V h = +70 mV. The voltage-
dependent activation of single alamethicin channels with up to five
conductance states was observed. 23 The different conductance
states are defined by the number of monomers making up the pore
forming aggregate. Hence, from the results one can conclude that,
indeed, monomeric alamethicin helices can move laterally within
the nano-BLM to form conducting oligomers.
( c ) 2,2'-Bipyridine-Functionalized Peptidic Ion Channels
Based on this knowledge, it was the idea to control the helix
bundle formation of amphipathic helices in nano-BLMs. Thus, we
synthesized an Į-helical amphipathic peptide with the sequence
H 2 N-(LeuSerSerLeuLeuSerLeu) 3 CONH 2 , to which a bipyridine
moiety with a spacer of 7 carbon atoms was attached to the N-
terminus, 58 in order to answer the question if it is possible to con-
trol the conductance behaviour of the peptide by complexation of
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