E
c
−
E
m
=d
MIN
see Section 1. A candidate phys- ical mechanism for d
MIN
is the specific potential energy difference between the membrane mi-
crodomain and the ion-channel protein required to thermodynamically constrain the protein to the
lower-potential-energy a
-helix conformation
closed state. In this manner, the duration of the channel open state, and thus, neuron spike fre-
quency macroscopic output are directly regu- lated by the molecular-ensemble search. Clearly,
the search could be prolonged or varied by spa- tial-temporal variation in ion-channel gatings fol-
lowing the initial perturbation input. The implications of the latter property will be dis-
cussed in Section 4.
4. Potential experiments
Can quantum computing in a model membrane be experimentally investigated? Clearly, we believe
that the answer is yes, but our optimism is tem- pered by an awareness of technical challenges. In
our laboratory, we are designing a set of artificial- membrane spectroscopy experiments based on our
computational evidence for ethylenic stacking and polarization. It is our intention to investigate
membrane-molecular regulation of a ligand-gated ion channel embedded in a model liposome sys-
tem. In the first stage of the experiments, we will obtain open-channel and closed-channel spectro-
scopic read-outs of the liposome and the embed- ded
receptor through
the use
of ‘caged’
L
-glutamate. Difference spectra open-channel – closed-channel will provide information regard-
ing changes in protein-lipid interactions as well as alterations in microdomain lipid organization. We
predict that this protocol will reveal an inverse correlation between duration of channel opening
and PUFA clustering in the lipid bilayer. See the anesthetic-epileptic
opposition discussion
in Vreugdenhil et al., 1996. These experiments will
also permit determination of PUFA ethylenic bond polarizability during permeant ion move-
ment. Closely related to this set of experiments is a subsequent set of measurements involving
fluorescence resonance energy transfer FRET, a technique widely utilized to investigate lipid struc-
ture and dynamics in membranes Edidin, 1989. Using FRET, we will monitor the distance be-
tween a fluorescein donor and a tetramethylrho- damine acceptor as a function of ion-channel
activity. We predict that acceptor-donor distances will be reduced in direct relation to PUFA con-
centration, a prediction consistent with the hy- pothesis of hydrophobic mismatch and lipid
selectivity.
A second stage of experimentation would in- volve evaluating the adaptation of the system to
increasing input complexity Garey and Johnson, 1979; Wallace, 1989, 1993, 1995; Wallace and
Price, 1999. Through the use of Raman and FRET techniques, the computational limit of
membrane molecular response minimum local potential energy search to gatings mediated via
caged glutamate of an increasing number of re- ceptors could be instrumentally identified as a
plateau response in the spectroscopic read-out Wallace and Price, 1999.
5. Conclusion
