Kinetic, thermodynamic, and mechanistic patterns for free (unbound) cytochrome c at Au/SAM junctions: impact of electronic coupling, hydrostatic pressure, and stabilizing/denaturing additives

Combined kinetic (electrochemical) and thermodynamic (calorimetric) investigations were performed for an unbound (intact native-like) cytochrome c (CytC) freely diffusing to and from gold electrodes modified by hydroxyl-terminated self-assembled monolayer films (SAMs), under a unique broad range of experimental conditions. Our approach included: 1) fine-tuning of the charge-transfer (CT) distance by using the extended set of Au-deposited hydroxyl-terminated alkanethiol SAMs [-S-(CH(2))(n)-OH] of variable thickness (n=2, 3, 4, 6, 11); 2) application of a high-pressure (up to 150 MPa) kinetic strategy toward the representative Au/SAM/CytC assemblies (n=3, 4, 6); 3) complementary electrochemical and microcalorimetric studies on the impact of some stabilizing and denaturing additives. We report for the first time a mechanistic changeover detected for "free" CytC by three independent kinetic methods, manifested through 1) the abrupt change in the dependence of the shape of the electron exchange standard rate constant (k(o)) versus the SAM thickness (resulting in a variation of estimated actual CT range within ca. 15 to 25 A including ca. 11 A of an "effective" heme-to-omega-hydroxyl distance). The corresponding values of the electronic coupling matrix element vary within the range from ca. 3 to 0.02 cm(-1); 2) the change in activation volume from +6.7 (n=3), to approximately 0 (n=4), and -5.5 (n=6) cm(3) mol(-1) (disclosing at n=3 a direct pressure effect on the protein's internal viscosity); 3) a "full" Kramers-type viscosity dependence for k(o) at n=2 and 3 (demonstrating control of an intraglobular friction through the external dynamic properties), and its gradual transformation to the viscosity independent (nonadiabatic) regime at n=6 and 11. Multilateral cross-testing of "free" CytC in a native-like, glucose-stabilized and urea-destabilized (molten-globule-like) states revealed novel intrinsic links between local/global structural and functional characteristics. Importantly, our results on the high-pressure and solution-viscosity effects, together with matching literature data, strongly support the concept of "dynamic slaving", which implies that fluctuations involving "small" solution components control the proteins' intrinsic dynamics and function in a highly cooperative manner as far as CT processes under adiabatic conditions are concerned.     

Free Diffusions and Matrix Models with Strictly Convex Interaction

We study solutions to the free stochastic differential equation , where V is a locally convex polynomial potential in m non-commuting variables and S an m-dimensional free Brownian motion. We prove that such free processes have a unique stationary distribution μV. When the potential V is self-adjoint, we show that the law μV is the limit law of a random matrix model, in which an m-tuple of self-adjoint matrices are chosen according to the law exp. If V = V_β depends on complex parameters , we prove that the moments of the law μV are analytic in β at least for those β for which V_β is locally convex. In particular, this gives information on the region of convergence of the generating function for the enumeration of related planar maps. We prove that the solution X_t has nice convergence properties with respect to the operator norm as t goes to infinity. This allows us to show that the C* and W* algebras generated by an m-tuple with law μV share many properties with those generated by a semi-circular system. Among them is the lack of projections, exactness, the Haagerup property, and embeddability into the ultrapower of the hyperfinite II₁ factor. We show that the microstates free entropy χ(μV ) is finite when V is self-adjoint. A corollary of these results is the fact that the support of the law of any self-adjoint polynomial in under the law μV is connected, vastly generalizing the case of a single random matrix. We also deduce from this dynamical approach that the convergence of the operator norms of independent matrices from the GUE proved by Haagerup and Thorbjornsen [HT] extends to the context of matrices interacting via a convex potential. Received: February 2007, Revision: July 2007, Accepted: July 2007     

An adaptive algorithm for efficient computation of level curves of surfaces

A new efficient algorithm for the computation of z?=?constant level curves of surfaces z?=?f(x,y) is proposed and tested on several examples. The set of z-level curves in a given rectangle of the (x,y)-plane is obtained by evaluating f on a first coarse square grid which is then adaptively refined by triangulation to eventually match a desired tolerance. Adaptivity leads to a considerable reduction in terms of evaluations of f with respect to uniform grid computation as in Matlab®’s contour. Furthermore, especially when the evaluation of f is computationally expensive, this reduction notably decreases the computational time. A comparison of performances is shown for two real-life applications such as the determination of stability charts and of ε??pseudospectra for linear time delay systems. The corresponding Matlab code is also discussed.     

Acoustic particle velocity horns

The paper considers receiving acoustic horns designed for particle velocity amplification and suitable for use in vector sensing applications. Unlike conventional horns, designed for acoustic pressure amplification, acoustic velocity horns (AVHs) deliver significant velocity amplification even when the overall size of the horn is much less than an acoustic wavelength. An AVH requires an open-ended configuration, as compared to pressure horns which are terminated at the throat. The appropriate formulation, based on Webster's one-dimensional horn equation, is derived and analyzed for single conical and exponential horns as well as for double-horn configurations. Predicted horn amplification factors (ratio of mouth-to-throat radii) were verified using numerical modeling. It is shown that three independent geometrical parameters principally control a horn's performance: length l, throat radius R(1), and flare rate. Below a predicted resonance region, velocity amplification is practically independent of frequency. Acoustic velocity horns are naturally directional, providing maximum velocity amplification along the boresight.     

On a Classical Limit of <Emphasis Type="Italic">q</Emphasis>-Deformed Whittaker Functions

Previously, we derive a representation of q-deformed \({\mathfrak{gl}_{\ell+1}}\) -Whittaker function as a sum over Gelfand–Zetlin patterns. This representation provides an analog of the Shintani–Casselman–Shalika formula for q-deformed \({\mathfrak{gl}_{\ell+1}}\) -Whittaker functions. In this note, we provide a derivation of the Givental integral representation of the classical \({\mathfrak{gl}_{\ell+1}}\) -Whittaker function as a limit q → 1 of the sum over the Gelfand–Zetlin patterns representation of the q-deformed \({\mathfrak{gl}_{\ell+1}}\) -Whittaker function. Thus, Givental representation provides an analog the Shintani–Casselman–Shalika formula for classical Whittaker functions.     

Polyvalent Transition-State Analogues of Sialyl Substrates Strongly Inhibit Bacterial Sialidases**

Bacterial sialidases (SA) are validated drug targets expressed by common human pathogens such as Streptococcus pneumoniae, Vibrio cholerae, or Clostridium perfringens. Noncovalent inhibitors of bacterial SA capable of reaching the submicromolar level are rarely reported. In this work, multi- and polyvalent compounds are developed, based on the transition-state analogue 2-deoxy-2,3-didehydro-N-acetylneuraminic (DANA). Poly-DANA inhibits the catalytic activity of SA from S. pneumoniae (NanA) and the symbiotic microorganism B. thetaiotaomicron (BtSA) at the picomolar and low nanomolar levels (expressed in moles of molecules and of DANA, respectively). Each DANA grafted to the polymer surpasses the inhibitory potential of the monovalent analogue by more than four orders of magnitude, which represents the highest multivalent effect reported so far for an enzyme inhibition. The synergistic interaction is shown to operate exclusively in the catalytic domain, and not in the flanked carbohydrate-binding module (CBM). These results offer interesting perspectives for the multivalent inhibition of other SA families lacking a CBM, such as viral, parasitic, or human SA.     

Forty years of theory-inspired experiments on charge-transfer via solutions and electrodes: the Georgian accents

Journal of Solid State Electrochemistry - This scholarly review, which also contains some specific historical details, is written by a few of researchers representing two generations succeeding the...     

Unprecedented Route to Ordered Polyaniline: Direct Synthesis of Highly Crystalline Fibrillar Films with Strong π‐π Stacking Alignment

Films of polyaniline (PANI) featuring about 80% crystallinity and characterised with strong π‐π stacking alignment parallel to the film surface have been obtained directly after the original synthesis upon simple drying of the aqueous PANI suspension. A strong anisotropy in the growth of the nano‐sized crystals produced during the synthesis results in the formation of micrometer‐length fibrils perpendicular to the film surface in the course of water evaporation. The regular intercalation of water molecules between the PANI chains seems to be crucial for their ordering throughout the synthesis and film formation.