Though devised by nature to regulate metabolite transport, mesoscopic channels are routinely studied in terms of their ability to conduct small ions. To address their functional properties, that is, their ability to transfer small solutes other than water and small ions, we use the Molecular Coulter Counter approach. This approach, introduced in our previous work with ion channels and small water-soluble polymers, permits one to study solute partitioning into and solute dynamics within the confines of the channel pore. We have applied this technique to study ATP transport through a single mitochondrial channel, VDAC. We have found that at high salt concentrations, the addition of ATP reduces both solution specific conductivity and channel conductance, but the effect on the channel is several times stronger. ATP addition also generates an excess noise in the ionic current through the channel. Analyzing the ATP-induced effects we show a pronounced attraction between ATP molecules and VDAC's aqueous pore (about 2 kT per molecule) and calculate a diffusion coefficient of ATP molecules within pore confines (D = (1.6-3.3)10-11m2/s). This value is one order of magnitude smaller than the ATP diffusion coefficient in the bulk, but is high enough to suggest that VDAC is able to mediate ATP efflux from mitochondria. Thus, we demonstrate that it is possible to study metabolite transport at the level of a single ion channel reconstituted into a planar bilayer. II. To understand the influence of membrane surface charge on ion channel functioning, as a first step, we studied mobile charge distribution in the vicinity of lipid planar bilayer by using a (small) cation-selective channel gramicidin A. Changing surface charge by two techniques, titration of the lipid charge through bulk solution pH and dilution of a charged lipid by neutral, we show that a previously unrecognized approach, Gibbs dividing surface construction for the counter-charge layer, describes our findings well. III. We continued our work on the signal transduction in molecular reactions in the presence of an external noise. We have found noise-facilitated signal transduction, Stochastic Resonance (SR), in a very general model -- a random pulse train where the probability of pulse generation is non-linearly dependent on an input which is composed of a signal plus random noise. The model suggests that SR is an inherent property of every biochemical reaction that can be characterized by an activation barrier modulated by some external parameter. We conclude that Stochastic Resonance is a universal statistical law rather than a peculiar property of a particular system as it was believed previously.""""""""
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| Nestorovich, Ekaterina M; Danelon, Christophe; Winterhalter, Mathias et al. (2002) Designed to penetrate: time-resolved interaction of single antibiotic molecules with bacterial pores. Proc Natl Acad Sci U S A 99:9789-94 |
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| Rostovtseva, Tatiana K; Nestorovich, Ekaterina M; Bezrukov, Sergey M (2002) Partitioning of differently sized poly(ethylene glycol)s into OmpF porin. Biophys J 82:160-9 |
| Kullman, Lisen; Winterhalter, Mathias; Bezrukov, Sergey M (2002) Transport of maltodextrins through maltoporin: a single-channel study. Biophys J 82:803-12 |
| Malev, Valery V; Schagina, Ludmila V; Gurnev, Philip A et al. (2002) Syringomycin E channel: a lipidic pore stabilized by lipopeptide? Biophys J 82:1985-94 |
| Aguilella, V M; Bezrukov, S M (2001) Alamethicin channel conductance modified by lipid charge. Eur Biophys J 30:233-41 |
| Ruszczynski, Peter S.; Kish, Laszlo B.; Bezrukov, Sergey M. (2001) Noise-assisted traffic of spikes through neuronal junctions. Chaos 11:581-586 |
| Rand, R P; Parsegian, V A; Rau, D C (2000) Intracellular osmotic action. Cell Mol Life Sci 57:1018-32 |
| Bezrukov, S M; Winterhalter, M (2000) Examining noise sources at the single-molecule level: 1/f noise of an open maltoporin channel. Phys Rev Lett 85:202-5 |
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