The dynamics and free energy of polymers partitioning into a nanoscale pore were investigated using channels formed by Staphylococcus aureus alpha-toxin. Neutral linear polymer, polyethyleneglycol (PEG), was used in this work because of its well-studied physical and chemical properties, remarkably small persistence length, and commercial availability in a convenient range of molecular weights. The free energy of polymer confinement in the pore deduced from our analysis differs significantly from predictions of scaling theory. The scaling approach yields a much weaker dependence of partitioning on the polymer weight but, surprisingly, gives a correct estimate for the polymer size corresponding to one kappaT of energy. The characteristic size determined in this manner distinguishes between polymers that partition into and those that are entropically excluded from the pore. Our results also suggest that PEG has an attractive interaction with the pore. This is in striking contrast to what one would expect if the pore is lined exclusively with hydrophilic amino acids. If our conclusion is true, then the functional role of these residues is intriguing. One possible speculation is that they provide a mechanism to disrupt the water structure inside this pore to facilitate the transport of solutes. We extended our work on the signal transduction properties of voltage- dependent ion channels in the presence of an external electric noise source. We found noise-facilitated signal transduction, stochastic resonance, in a very general model -- a random pulse train where the probability of pulse generation is exponentially dependent on an input which is composed of a sine-wave signal plus random noise. Analysis of the statistical properties of such a pulse train yields the following features: 1. Threshold-free response -- the ability to transfer small signals with a transduction coefficient independent of signal amplitude; 2. Noise-facilitated signal transduction -- the property to increase the output signal amplitude by addition of noise to the system input; 3. Noise-induced improvement in the output SNR -- the existence of particular input noise levels that optimize the output signal quality. The model offers a quantitative description for the experimental results found for voltage-dependent ion channels reconstituted into an artificial planar lipid bilayer membrane. Moreover, the theory predicts the existence of SR in all systems that can be represented by a random pulse train with exponential statistics. Since random pulse trains describe almost all physicochemical processes at molecular level, stochastic resonance is probably much more universal phenomenon that it was believed previously.

Agency
National Institute of Health (NIH)
Institute
Center for Information Technology (CIT)
Type
Intramural Research (Z01)
Project #
1Z01CT000242-06
Application #
6161674
Study Section
Special Emphasis Panel (LSB)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Center for Information Technology
Department
Type
DUNS #
City
State
Country
United States
Zip Code