Bird's-eye view on Noise-Based Logic

Noise-based logic is a practically deterministic logic scheme inspired by the randomness of neural spikes and uses a system of uncorrelated stochastic processes and their superposition to represent the logic state. We briefly discuss various questions such as (i) What does practical determinism mean? (ii) Is noise-based logic a Turing machine? (iii) Is there hope to beat (the dreams of) quantum computation by a classical physical noise-based processor, and what are the minimum hardware requirements for that? Finally, (iv) we address the problem of random number generators and show that the common belief that quantum number generators are superior to classical (thermal) noise-based generators is nothing but a myth.Comment: paper in pres

Blocker effect on diffusion resistance of a membrane channel. Dependence on the blocker geometry

Being motivated by recent progress in nanopore sensing, we develop a theory of the effect of large analytes, or blockers, trapped within the nanopore confines, on diffusion flow of small solutes. The focus is on the nanopore diffusion resistance which is the ratio of the solute concentration difference in the reservoirs connected by the nanopore to the solute flux driven by this difference. Analytical expressions for the diffusion resistance are derived for a cylindrically symmetric blocker whose axis coincides with the axis of a cylindrical nanopore in two limiting cases where the blocker radius changes either smoothly or abruptly. Comparison of our theoretical predictions with the results obtained from Brownian dynamics simulations shows good agreement between the two

Conductance of Ideally Cation Selective Channel Depends on Anion Type

poster abstractGramicidin A (gA) is a transmembrane, cation selective ion channel that has been used in many biophysical studies of lipid bilayers, in particular for investigations of lipid-protein interactions and membrane electrostatics. In addition, it was found that ionic interactions with neutral lipid membranes also affect the kinetics of gA channels. Here we report measurements of gA ion-channels for a series of sodium and potassium salts that show an anion-dependence of gA conductance. We find that gA conductance varies significantly with the anion type with ClO4 and SCN producing distinctly larger conductance values than Cl, F, and H2PO4. These results can provide new insights into ion-lipid membrane interactions and ion channel functions in general

Fungicidal Activities and Mechanisms of Action of Pseudomonas syringae pv. syringae Lipodepsipeptide Syringopeptins 22A and 25A

The plant-associated bacterium Pseudomonas syringae pv. syringae simultaneously produces two classes of metabolites: the small cyclic lipodepsinonapeptides such as the syringomycins and the larger cyclic lipodepsipeptide syringopeptins SP22 or SP25. The syringomycins inhibit a broad spectrum of fungi (but particularly yeasts) by lipid-dependent membrane interaction. The syringopeptins are phytotoxic and inhibitory to Gram-positive bacteria. In this study, the fungicidal activities of two major syringopeptins, SP22A and SP25A, and their mechanisms of action were investigated and compared to those of syringomycin E. SP22A and SP25A were observed to inhibit the fungal yeasts Saccharomyces cerevisiae and Candida albicans although less effectively than syringomycin E. S. cerevisiae mutants defective in ergosterol and sphingolipid biosyntheses were less susceptible to SP22A and SP25A but the relative inhibitory capabilities of SRE vs. SP22A and SP25A were maintained. Similar differences were observed for capabilities to cause cellular K+ and Ca2+ fluxes in S. cerevisiae. Interestingly, in phospholipid bilayers the syringopeptins are found to induce larger macroscopic ionic conductances than syringomycin E but form single channels with similar properties. These findings suggest that the syringopeptins target the yeast plasma membrane, and, like syringomycin E, employ a lipid-dependent channel-forming mechanism of action. The differing degrees of growth inhibition by these lipodepsipeptides may be explained by differences in their hydrophobicities. The more hydrophobic SP22A and SP25A might interact more strongly with the yeast cell wall that would create a selective barrier for their incorporation into the plasma membrane

Phosphorylation of Voltage-Dependent Anion Channel by Serine/Threonine Kinases Governs Its Interaction with Tubulin

Tubulin was recently found to be a uniquely potent regulator of the voltage-dependent anion channel (VDAC), the most abundant channel of the mitochondrial outer membrane, which constitutes a major pathway for ATP/ADP and other metabolites across this membrane. Dimeric tubulin induces reversible blockage of VDAC reconstituted into a planar lipid membrane and dramatically reduces respiration of isolated mitochondria. Here we show that VDAC phosphorylation is an important determinant of its interaction with dimeric tubulin. We demonstrate that in vitro phosphorylation of VDAC by either glycogen synthase kinase-3β (GSK3β) or cAMP-dependent protein kinase A (PKA), increases the on-rate of tubulin binding to the reconstituted channel by orders of magnitude, but only for tubulin at the cis side of the membrane. This and the fact the basic properties of VDAC, such as single-channel conductance and selectivity, remained unaltered by phosphorylation allowed us to suggest the phosphorylation regions positioned on the cytosolic loops of VDAC and establish channel orientation in our reconstitution experiments. Experiments on human hepatoma cells HepG2 support our conjecture that VDAC permeability for the mitochondrial respiratory substrates is regulated by dimeric tubulin and channel phosphorylation. Treatment of HepG2 cells with colchicine prevents microtubule polymerization, thus increasing dimeric tubulin availability in the cytosol. Accordingly, this leads to a decrease of mitochondrial potential measured by assessing mitochondrial tetramethylrhodamine methyester uptake with confocal microscopy. Inhibition of PKA activity blocks and reverses mitochondrial depolarization induced by colchicine. Our findings suggest a novel functional link between serine/threonine kinase signaling pathways, mitochondrial respiration, and the highly dynamic microtubule network which is characteristic of cancerogenesis and cell proliferation

Cation-selective channel is regulated by anions according to their Hofmeister ranking

Specificity of small ions, the Hofmeister ranking, is long-known and has many applications including medicine. Yet it evades consistent theoretical description. Here we study the effect of Hofmeister anions on gramicidin A channels in lipid membranes. Counterintuitively, we find that conductance of this perfectly cation-selective channel increases about two-fold in the H2PO4−<Cl−≈Br−≈NO3−<ClO4−<SCN− series. Channel dissociation kinetics show even stronger dependence, with the dwell time increasing ~20-fold. While the conductance can be quantitatively explained by the changes in membrane surface potential due to exclusion of kosmotropes from (or accumulation of chaotropes at) the surface, the kinetics proved to be more difficult to treat. We estimate the effects of changes in the energetics at the bilayer surfaces on the channel dwell time, concluding that the change would have to be greater than typically observed for the Hofmeister effect outside the context of the lipid bilayer., Ion specificity and, in particular, the distinctive effects of anions in salt-induced protein precipitation have been known since the 1880’s, when Franz Hofmeister established the ranking of anions in their ability to regulate egg yolk protein water solubility []. Experimental and theoretical studies have given a detailed empirical picture of the phenomenon, the nature of the ionic interactions with the surfaces leading to the Hofmeister effect is still under debate []. The only consensus is that it cannot be explained by standard theories of electrolytes. For example, bromide is unique in that its salts were recognized as a drug to treat epilepsy a couple of dozen years before Hofmeister’s studies [] and they are still in use to treat specific types of refractory seizures in children [], but the mechanism of their action remains elusive., , Hofmeister effect studied with a nanopore in a neutral lipid membrane. Rather unexpectedly, we find that conductance of a purely cation-selective peptide pore is regulated by anions in correlation with their position in the Hofmeister series. Moreover, the pore conformational dynamics are highly sensitive to the anion species. We relate both effects to preferential depletion of kosmotropic anions (accumulation of chaotropic anions) at the membrane-water interface