Erythrocytes membrane fluidity changes induced by adenylyl cyclase cascade activation: study using fluorescence recovery after photobleaching.

In this study, fluorescence recovery after photobleaching (FRAP) experiments were performed on RBC labeled by lipophilic fluorescent dye CM-DiI to evaluate the role of adenylyl cyclase cascade activation in changes of lateral diffusion of erythrocytes membrane lipids. Stimulation of adrenergic receptors with epinephrine (adrenaline) or metaproterenol led to the significant acceleration of the FRAP recovery, thus indicating an elevated membrane fluidity. The effect of the stimulation of protein kinase A with membrane-permeable analog of cAMP followed the same trend but was less significant. The observed effects are assumed to be driven by increased mobility of phospholipids resulting from the weakened interaction between the intermembrane proteins and RBC cytoskeleton due to activation of adenylyl cyclase signaling cascade.

Adsorption of semiflexible wormlike polymers to a bar and their double-chain complex formation.

We theoretically study pairing (double-strand complexation) of semiflexible wormlike chains (WLC) due to their side-to-side attraction. Considering binding of two WLCs of high stiffness we start with the case of infinite stiffness of one chain which is replaced with a straight bar. A combination of the quantitative transfer matrix approach with scaling arguments in terms of trains, loops of different sizes, tails and supertrains allowed us to characterize all the regimes of semiflexible chain adsorption on a bar. In particular, we predict a self-similar monomer concentration profile c(r) ∝ r-10/3 near the bar (at distances r below the chain Kuhn length l) at the critical point for adsorption. Such localized critical profile leads to a sharp adsorption transition. Furthermore, we found that supertrains serve as the basic structural elements in WLC complexes leading to bridging, network formation and condensation of semiflexible polymers in dilute solutions. Polymer collapse (precipitation) and redissolution on increasing attraction strength are predicted in qualitative agreement with experiments on aqueous solutions of DNA and F-actin.

Strain correlation functions in isotropic elastic bodies: large wavelength limit for two-dimensional systems.

Strain correlation functions in two-dimensional isotropic elastic bodies are shown both theoretically (using the general structure of isotropic tensor fields) and numerically (using a glass-forming model system) to depend on the coordinates of the field variable (position vector r in real space or wavevector q in reciprocal space) and thus on the direction of the field vector and the orientation of the coordinate system. Since the fluctuations of the longitudinal and transverse components of the strain field in reciprocal space are known in the long-wavelength limit from the equipartition theorem, all components of the correlation function tensor field are imposed and no additional physical assumptions are needed. An observed dependence on the field vector direction thus cannot be used as an indication for anisotropy or for a plastic rearrangement. This dependence is different for the associated strain response field containing also information on the localized stress perturbation.

Correlations of tensor field components in isotropic systems with an application to stress correlations in elastic bodies.

Correlation functions of components of second-order tensor fields in isotropic systems can be reduced to an isotropic fourth-order tensor field characterized by a few invariant correlation functions (ICFs). It is emphasized that components of this field depend in general on the coordinates of the field vector variable and thus on the orientation of the coordinate system. These angular dependencies are distinct from those of ordinary anisotropic systems. As a simple example of the procedure to obtain the ICFs we discuss correlations of time-averaged stresses in isotropic glasses where only one ICF in reciprocal space becomes a finite constant e for large sampling times and small wave vectors. It is shown that e is set by the typical size of the frozen-in stress components normal to the wave vectors, i.e., it is caused by the symmetry breaking of the stress for each independent configuration. Using the presented general mathematical formalism for isotropic tensor fields this finding explains in turn the observed long-range stress correlations in real space. Under additional but rather general assumptions e is shown to be given by a thermodynamic quantity, the equilibrium Young modulus E. We thus relate for certain isotropic amorphous bodies the existence of finite Young or shear moduli to the symmetry breaking of a stress component in reciprocal space.

Different types of spatial correlation functions for non-ergodic stochastic processes of macroscopic systems.

Focusing on non-ergodic macroscopic systems, we reconsider the variances [Formula: see text] of time averages [Formula: see text] of time-series [Formula: see text]. The total variance [Formula: see text] (direct average over all time series) is known to be the sum of an internal variance [Formula: see text] (fluctuations within the meta-basins) and an external variance [Formula: see text] (fluctuations between meta-basins). It is shown that whenever [Formula: see text] can be expressed as a volume average of a local field [Formula: see text] the three variances can be written as volume averages of correlation functions [Formula: see text], [Formula: see text] and [Formula: see text] with [Formula: see text]. The dependences of the [Formula: see text] on the sampling time [Formula: see text] and the system volume V can thus be traced back to [Formula: see text] and [Formula: see text]. Various relations are illustrated using lattice spring models with spatially correlated spring constants. .

Theory of length-scale dependent relaxation moduli and stress fluctuations in glass-forming and viscoelastic liquids.

The spatiotemporal correlations of the local stress tensor in supercooled liquids are studied both theoretically and by molecular dynamics simulations of a two-dimensional (2D) polydisperse Lennard-Jones system. Asymptotically exact theoretical equations defining the dynamical structure factor and all components of the stress correlation tensor for low wave-vector q are presented in terms of the generalized (q-dependent) shear and longitudinal relaxation moduli, G(q, t) and K(q, t). We developed a rigorous approach (valid for low q) to calculate K(q, t) in terms of certain bulk correlation functions (for q = 0), the static structure factor S(q), and thermal conductivity κ. The proposed approach takes into account both the thermostatting effect and the effect of polydispersity. The theoretical results for the (q, t)-dependent stress correlation functions are compared with our simulation data, and an excellent agreement is found for qb̄≲0.5 (with b̄ being the mean particle diameter) both above and below the glass transition without any fitting parameters. Our data are consistent with recently predicted (both theoretically and by simulations) long-range correlations of the shear stress quenched in heterogeneous glassy structures.

Simple models for strictly non-ergodic stochastic processes of macroscopic systems.

We investigate simple models for strictly non-ergodic stochastic processes [Formula: see text] (t being the discrete time step) focusing on the expectation value v and the standard deviation [Formula: see text] of the empirical variance [Formula: see text] of finite time series [Formula: see text]. [Formula: see text] is averaged over a fluctuating field [Formula: see text] ([Formula: see text] being the microcell position) characterized by a quenched spatially correlated Gaussian field [Formula: see text]. Due to the quenched [Formula: see text]-field [Formula: see text] becomes a finite constant, [Formula: see text], for large sampling times [Formula: see text]. The volume dependence of the non-ergodicity parameter [Formula: see text] is investigated for different spatial correlations. Models with marginally long-ranged [Formula: see text]-correlations are successfully mapped on shear stress data from simulated amorphous glasses of polydisperse beads.

Relaxation moduli of glass-forming systems: temperature effects and fluctuations.

Equilibrium and dynamical properties of a two-dimensional polydisperse colloidal model system are characterized by means of molecular dynamics (MD) and Monte Carlo (MC) simulations. We employed several methods to prepare quasi-equilibrated systems: in particular, by slow cooling and tempering with MD (method SC-MD), and by tempering with MC dynamics involving swaps of particle diameters (methods Sw-MD, Sw-MC). It is revealed that the Sw-methods are much more efficient for equilibration below the glass transition temperature Tg leading to denser and more rigid systems which show much slower self-diffusion and shear-stress relaxation than their counterparts prepared with the SC-MD method. The shear-stress relaxation modulus G(t) is obtained based on the classical stress-fluctuation relation. We demonstrate that the α-relaxation time τα obtained using a time-temperature superposition of G(t) shows a super-Arrhenius behavior with the VFT temperature T0 well below Tg. We also derive novel rigorous fluctuation relations providing isothermic and adiabatic compression relaxation moduli in the whole time range (including the short-time inertial regime) based on correlation data for thermostatted systems. It is also shown that: (i) the assumption of Gaussian statistics for stress fluctuations leads to accurate predictions of the variances of the fluctuation moduli for both shear (µF) and compression (ηF) at T⪆Tg. (ii) The long-time (quasi-static) isothermic and adiabatic moduli increase on cooling faster than the affine compression modulus ηA, and this leads to a monotonic temperature dependence of ηF which is qualitatively different from µF(T) showing a maximum near Tg.

General relations to obtain the time-dependent heat capacity from isothermal simulations.

It is well-known that time-dependent correlation functions related to temperature and energy can crucially depend on the thermostatting mechanism used in computer simulations of molecular systems. We argue, however, that linear response functions must be considered as universal properties of physical systems. This implies that the classical fluctuation equation for the transient heat capacity, cv(t), is not applicable to the thermostatted molecular dynamics (apart from long enough times). To improve on this point, we derive a number of exact general expressions for the frequency-dependent heat capacity in terms of energy correlation functions, valid for the Nosé-Hoover and some other thermostats. We also establish a general relation between auto- and cross correlation functions of energy and temperature. Recommendations on how to use these relations to maximize the numerical precision are provided. It is demonstrated that our approach allows us to obtain cv(t) for a supercooled liquid system with high precision and over many decades in time reflecting all pertinent relaxation processes.

Fluctuations of non-ergodic stochastic processes.

We investigate the standard deviation [Formula: see text] of the variance [Formula: see text] of time series [Formula: see text] measured over a finite sampling time [Formula: see text] focusing on non-ergodic systems where independent "configurations" c get trapped in meta-basins of a generalized phase space. It is thus relevant in which order averages over the configurations c and over time series k of a configuration c are performed. Three variances of [Formula: see text] must be distinguished: the total variance [Formula: see text] and its contributions [Formula: see text], the typical internal variance within the meta-basins, and [Formula: see text], characterizing the dispersion between the different basins. We discuss simplifications for physical systems where the stochastic variable x(t) is due to a density field averaged over a large system volume V. The relations are illustrated for the shear-stress fluctuations in quenched elastic networks and low-temperature glasses formed by polydisperse particles and free-standing polymer films. The different statistics of [Formula: see text] and [Formula: see text] are manifested by their different system-size dependences.

Ensemble fluctuations matter for variances of macroscopic variables.

Extending recent work on stress fluctuations in complex fluids and amorphous solids we describe in general terms the ensemble average [Formula: see text] and the standard deviation [Formula: see text] of the variance [Formula: see text] of time series [Formula: see text] of a stochastic process x(t) measured over a finite sampling time [Formula: see text]. Assuming a stationary, Gaussian and ergodic process, [Formula: see text] is given by a functional [Formula: see text] of the autocorrelation function h(t). [Formula: see text] is shown to become large and similar to [Formula: see text] if [Formula: see text] corresponds to a fast relaxation process. Albeit [Formula: see text] does not hold in general for non-ergodic systems, the deviations for common systems with many microstates are merely finite-size corrections. Various issues are illustrated for shear-stress fluctuations in simple coarse-grained model systems.

Nanobodies Are Potential Therapeutic Agents for the Ebola Virus Infection.

Ebola fever is an acute, highly contagious viral disease with a mortality rate that can reach 90%. There are currently no licensed therapeutic agents specific to Ebola in the world. Monoclonal antibodies (MAbs) with viral-neutralizing activity and high specificity to the Ebola virus glycoprotein (EBOV GP) are considered as highly effective potential antiviral drugs. Over the past decade, nanobodies (single-domain antibodies, non-canonical camelid antibodies) have found wide use in the diagnosis and treatment of various infectious and non-infectious diseases. In this study, a panel of nanobodies specifically binding to EBOV GP was obtained using recombinant human adenovirus 5, expressing GP (Ad5-GP) for alpaca (Vicugna pacos) immunization, for the first time. Based on specific activity assay results, affinity constants, and the virus-neutralizing activity against the recombinant vesicular stomatitis virus pseudotyped with EBOV GP (rVSV-GP), the most promising clone (aEv6) was selected. The aEv6 clone was then modified with the human IgG1 Fc fragment to improve its pharmacokinetic and immunologic properties. To assess the protective activity of the chimeric molecule aEv6-Fc, a lethal model of murine rVSV-GP infection was developed by using immunosuppression. The results obtained in lethal model mice have demonstrated the protective effect of aEv6-Fc. Thus, the nanobody and its modified derivative obtained in this study have shown potential protective value against Ebola virus.

Composition fluctuations in polydisperse liquids: Glasslike effects well above the glass transition.

We study a two-dimensional glass-forming system of slightly polydisperse (LJ) particles using molecular dynamics simulations and demonstrate that in the liquid regime (well above the vitrification temperature) this model shows a number of features typical of the glass transition: (i) the relation between compressibility and structure factor S(q) is strongly violated; (ii) the dynamical structure factor S(q,t) at low q shows a two-step relaxation; (iii) the time-dependent heat capacity c_{v}(t) shows a long-time power-law tail. We show that these phenomena can be rationalized with the idea of composition fluctuations and provide a quantitative theory for the effects (i) and (ii). It implies that such effects must be inherent in all polydisperse colloidal models, including binary LJ mixtures.

The concept of strongly interacting groups in self-assembly of soft matter.

Amphiphilic molecules in solution typically produce structures coming from cooperative interactions of many synergetically acting functional units. If all essential interactions are weak, the structure can be treated theoretically based on a free energy expansion for small interaction parameters. However, most self-assembling soft matter systems involve strong specific interactions of functional units leading to qualitatively new structures of highly soluble micellar or fibrillar aggregates. Here we focus on the systems with the so-called strongly interacting groups (SIGs) incorporated into unimer molecules and discuss the effects of packing frustrations and unimer chirality as well as the origins of spontaneous morphological chirality in the case of achiral unimers. We describe several theoretical approaches (overcoming the limitations of weak interaction models) including the concepts of super-strong segregation, geometrical mismatch and orientational frustration. We also review some recently developed phenomenological theories of surfactant membranes and multiscale hierarchical approaches based on all-atomic modeling of packing structures of amphiphilic molecules with SIGs. In particular, we discuss self-assembling structures in systems possessing simultaneously several distinct types of SIGs: solutions of beta-sheet oligopeptides (showing different fibrillar morphologies), aromatic diamide-ester molecules (forming membranes, helical ribbons and tubules), and triarylamine amide derivatives (producing light-controlled supramolecular nanowires).

Long-range stress correlations in viscoelastic and glass-forming fluids.

A simple and rigorous approach to obtain stress correlations in viscoelastic liquids (including supercooled liquid and equilibrium amorphous systems) is proposed. The long-range dynamical correlations of local shear stress are calculated and analyzed in 2-dimensional space. It is established how the long-range character of the stress correlations gradually emerges as the relevant dynamical correlation length l grows in time. The correlation range l is defined by momentum propagation due to acoustic waves and vorticity diffusion which are the basic mechanisms for transmission of shear stress perturbations. We obtain the general expression defining the time- and distance-dependent stress correlation tensor in terms of material functions (generalized relaxation moduli). The effect of liquid compressibility is quantitatively analyzed; it is shown to be important at large distances and/or short times. The revealed long-range stress correlation effect is shown to be dynamical in nature and unconnected with static structural correlations in liquids (correlation length ξs). Our approach is based on the assumption that ξs is small enough as reflected in weak wave-number dependencies of the generalized relaxation moduli. We provide a simple physical picture connecting the elucidated long-range fluctuation effect with anisotropic correlations of the (transient) inherent stress field, and discuss its implications.

Anomalous sound attenuation in Voronoi liquid.

The physics of simple fluids in the hydrodynamic limit and notably the connection between the proper microscopic scales and the macroscopic hydrodynamical description are nowadays well understood. In particular, the three peak shape of the dynamical structure factor S(k,ω) is a universal feature, as well as the k-dependence of the peak position (∝k) and width ∝k2, the latter accounting for the sound attenuation rate. In this paper, we present a theoretical model of monodisperse fluid, whose interactions are defined via the Voronoi tessellations of the configurations [called the Voronoi liquid and first studied in Ruscher et al., Europhys. Lett. 112, 66003 (2015)], which displays at low temperatures a marked violation of the universal features of S(k,ω) with a sound attenuation rate only ∝k. This anomalous behaviour, which apparently violates the basic symmetries of the liquid state, is traced back to the existence of a time scale which is both short enough for the viscoelastic features of the liquid to impact the relaxational dynamics and however long enough for the momentum diffusion to be substantially slower than the sound propagation on that characteristic time.

Adsorption of flexible polyelectrolytes on charged surfaces.

Adsorption of weakly charged polyelectrolyte (PE) chains from dilute solution on an oppositely charged surface is studied using the self-consistent mean-field approach. The structure of the adsorbed polymer layer and its excess charge are analyzed in the most important asymptotic and intermediate regimes both analytically and numerically. Different regimes of surface charge compensation by PE chains including partial and full charge inversion are identified and discussed in terms of physical parameters like the magnitude of specific short-range interactions of PE segments with the surface, solvent quality and ionic strength. The effect of excluded-volume monomer interactions is considered quantitatively both in the marginally good and poor solvent regimes.

Theory of colloid depletion stabilization by unattached and adsorbed polymers.

The polymer-induced forces between colloidal particles in a semidilute or concentrated polymer solution are considered theoretically. This study is focussed on the case of partially adsorbing colloidal surfaces involving some attractive centers able to trap polymer segments. In the presence of free polymers the particles are covered by self-assembled fluffy layers whose structure is elucidated. It is shown that the free-polymer-induced interaction between the particles is repulsive at distances exceeding the polymer correlation length, and that this depletion repulsion can be strongly enhanced due to the presence of fluffy layers. This enhanced depletion stabilization mechanism (which works in tandem with a more short-range steric repulsion of fluffy layers) can serve on its own to stabilize colloidal dispersions. More generally, we identify three main polymer-induced interaction mechanisms: depletion repulsion, depletion attraction, and steric repulsion. Their competition is analyzed both numerically and analytically based on an asymptotically rigorous mean-field theory. It is shown that colloid stabilization can be achieved by simply increasing the molecular weight of polymer additives, or by changing their concentration.

Thermodynamic nature of vitrification in a 1D model of a structural glass former.

We propose a new spin-glass model with no positional quenched disorder which is regarded as a coarse-grained model of a structural glass-former. The model is analyzed in the 1D case when the number N of states of a primary cell is large. For N → ∞, the model exhibits a sharp freezing transition of the thermodynamic origin. It is shown both analytically and numerically that the glass transition is accompanied by a significant growth of a static length scale ξ pointing to the structural (equilibrium) nature of dynamical slowdown effects in supercooled liquids.

[Regularities of the ubiquitous polyhostal microorganisms selection by the example of three taxa].

The investigation of the bacterial populations' heterogeneity contributes to the control of natural foci, causative agents of nosocomial infections, to the analysis of the microbial evolution. Multilocus sequence typing (MLST) was employed for the analysis of the diversity and features of the distribution of polyhostal ubiquitous microorganisms of the genera Burkholderia, Leptospira, and Listeria, which belong to three bacterial phyla: Proteobacteria, Spirochaetes, and Firmicutes. According to the bacterial samples analysis microbial genotypes prevalent and unique to Russia were identified; their occurrence in different Federal Regions was investigated; their similarity with global spread genotypes was appreciated. Obtained results allowed identifying common regularities of the selection of the microorganisms capable to cause the diseases of human and animals. The formation of genotypes that are most pathogenic for the host was demonstrated for all groups of bacteria. Leptospira spp. and Listeria monocytogenes strains with these genotypes have been circulating for a long time, being supported by natural foci. The formation of a wide variety of genotypes with different pathogenicity was demonstrated in the local geographic areas. In Russia, the zonal difference in all three groups of bacteria is most clearly traced to the Far Eastern Federal Region. The results are thought to contribute to analyzing the factors of selection and the phylogeny of the taxa under study.