Ensemble Behavior Research Articles

Ensemble Behavior of Actomyosin Crossbridges

Ensemble Behavior of Actomyosin Crossbridges

Membrane-Mediated Gramicidin Interactions Determine Peptide Clustering and Enhance Channel Formation

Gramicidin is a membrane channel-forming antibiotic that is thoroughly investigated. The peptide monomer is embedded into a single monolayer of a bilayer membrane. The through channel is formed by transmembrane dimerization of two peptide molecules. The details of the monomer interaction remain unknown. Using continuous elastic model we studied the interaction of two gramicidin monomers embedded into a lipid bilayer. The calculated dependencies of dimer formation frequency on membrane tension and channel lifetime on membrane thickness proved to be in perfect agreement with available experimental data. The energy profile of the interaction was calculated for peptides located in the same monolayer and in the opposite monolayers of lipid membrane. We found out that the energy of the system had a minimum when two gramicidin peptides were separated by a few nanometers for both cases. The calculated interaction energy profile was used to analyze the gramicidin molecules ensemble behavior. The simplest model of 2D Van der Waals gas was applied to calculate the critical temperature of the ensemble condensation. The calculated temperature was found to be approximately 3 times higher than the physiological temperature, which indicates that gramicidin peptides in membrane could form clusters, in agreement with recent experimental data. The designed elastic theory is general and may be used for the analysis of membrane-mediated interactions of the inclusions of different nature: transmembrane molecules, amphipathic peptides, etc. The work was supported by the Russian Foundation for Basic Research (project # 17-04-02070).

Elucidation of the structural stability and dynamics of heterogeneous intermediate ensembles in unfolding pathway of the N-terminal domain of TDP-43.

The N-terminal domain of the RNA binding protein TDP-43 (NTD) is essential to both physiology and proteinopathy; however, elucidation of its folding/unfolding still remains a major quest. In this study, we have investigated the biophysical behavior of intermediate ensembles employing all-atom molecular dynamics simulations in 8 M urea accelerated with high temperatures to achieve unfolded states in a confined computation time. The cumulative results of the 2.75 μs simulations show that unfolding of the NTD at 350 K evolves through different stable and meta-stable intermediate states. The free-energy landscape reveals two meta-stable intermediates (IN and IU) stabilized by non-native interactions, which are largely hydrophilic and highly energetically frustrated. A single buried tryptophan residue, W80, undergoes solvent exposure to different extents during unfolding; this suggests a structurally heterogeneous population of intermediate ensembles. Furthermore, the structure properties of the IN state show a resemblance to the molten globule (MG) state with most of the secondary structures intact. The unfolding of the NTD is initiated by the loss of β-strands, and the unfolded (U) states exhibit a population of non-native α-helices. These non-native unfolded intermediate ensembles may mediate protein oligomerization, leading to the formation of pathological, irreversible aggregates, characteristics of disease pathogenesis.

Engineering Synthetic Myosin Filaments Using DNA Nanotubes.

Throughout the cell, motor proteins work together to drive numerous molecular processes and functions. For example, ensembles of myosin motors collectively transport vesicles and organelles, maintain membrane homeostasis, and drive muscle contraction. Studying these motors in groups has become increasingly important with work demonstrating the emergence of ensemble behavior distinct from individual motor behavior. One powerful technique that has been used in the last decade is DNA nanotechnology, which provides precise control over spacing and organization of patterned motor proteins. Until recently, however, most studies combining DNA nanostructures and molecular motors have been confined to discrete DNA structures with limited attachment points for motor proteins. In this chapter, we describe a new approach for making synthetic motor filaments using DNA nanotubes. We present methods for preparing myosin VI-labeled nanotubes and testing these nanotubes using a general in vitro motility setup. Overall, these nanotubes can easily be used to study other large ensembles of molecular motors, such as muscle myosin or ciliary dynein, both proteins that work in large motor ensembles to drive key cellular functions.

Polynomial Ensembles and Recurrence Coefficients

Polynomial ensembles are determinantal point processes associated with (non necessarily orthogonal) projections onto polynomial subspaces. The aim of this survey article is to put forward the use of recurrence coefficients to obtain the global asymptotic behavior of such ensembles in a rather simple way. We provide a unified approach to recover well-known convergence results for real OP ensembles. We study the mutual convergence of the polynomial ensemble and the zeros of its average characteristic polynomial; we discuss in particular the complex setting. We also control the variance of linear statistics of polynomial ensembles and derive comparison results, as well as asymptotic formulas for real OP ensembles. Finally, we reinterpret the classical algorithm to sample determinantal point processes so as to cover the setting of non-orthogonal projection kernels. A few open problems are also suggested.

Direct Microscopic Analysis of Individual C60 Dimerization Events: Kinetics and Mechanisms.

Modern transition state theory states that the statistical behavior of a chemical reaction is the sum of individual chemical events that occur randomly. Statistical analysis of each event for individual molecules in a three-dimensional space however is practically impossible. We report here that kinetics and mechanisms of chemical reactions can be investigated by using a one-dimensional system where reaction events can be observed in situ and counted one by one using variable-temperature (VT) atomic-resolution transmission electron microscopy (TEM). We thereby provide direct proof that the ensemble behavior of random events conforms to the Rice-Ramsperger-Kassel-Marcus theory, as illustrated for [2 + 2] cycloaddition of C60 molecules in carbon nanotubes (CNTs). This method gives kinetic and structural information for different types of reactions occurring simultaneously in the microscopic view field, suggesting that the VT-TEM opens a new dimension of chemical kinetics research on molecules and their assemblies in their excited and ionized states. The study carried out at 393-493 K showed that pristine CNT primarily acts as a singlet sensitizer of the cycloaddition reaction that takes place with an activation energy of 33.5 ± 6.8 kJ/mol. On the other hand, CNT suffers electron damage of the conjugated system at 103-203 K and promotes a reactive radical cation path that takes place with an activation energy of only 1.9 ± 0.7 kJ/mol. The pre-exponential factor of the Arrhenius plot gave us further mechanistic insights.

Nonlinear consolidation in randomly heterogeneous highly compressible aquitards

Severe land subsidence due to groundwater extraction may occur in multiaquifer systems where highly compressible aquitards are present. The highly compressible nature of the aquitards leads to nonlinear consolidation where the groundwater flow parameters are stress-dependent. The case is further complicated by the heterogeneity of the hydrogeologic and geotechnical properties of the aquitards. The effect of realistic vertical heterogeneity of hydrogeologic and geotechnical parameters on the consolidation of highly compressible aquitards is investigated by means of one-dimensional Monte Carlo numerical simulations where the lower boundary represents the effect of an instant drop in hydraulic head due to groundwater pumping. Two thousand realizations are generated for each of the following parameters: hydraulic conductivity (K), compression index (C c), void ratio (e) and m (an empirical parameter relating hydraulic conductivity and void ratio). The correlation structure, the mean and the variance for each parameter were obtained from a literature review about field studies in the lacustrine sediments of Mexico City. The results indicate that among the parameters considered, random K has the largest effect on the ensemble average behavior of the system when compared to a nonlinear consolidation model with deterministic initial parameters. The deterministic solution underestimates the ensemble average of total settlement when initial K is random. In addition, random K leads to the largest variance (and therefore largest uncertainty) of total settlement, groundwater flux and time to reach steady-state conditions.

Changing Resources Available to Game Playing Agents: Another Relevant Design Factor in Agent Experiments

The iterated prisoner's dilemma is a simultaneous two-player game widely used in studies on cooperation and conflict. Recent research has demonstrated that a number of factors change the behavior of evolved agents in a manner not consistent with controlled studies. This study extends a preliminary exploration of the impact of changing the level of computational or informational resources available to game playing agents on their ensemble behavior. Both these categories of information are shown to have an impact on agent behavior. Four representations are studied: lookup tables, Markov chains, finite-state machines, and feed-forward neural nets. An assessment tool called the play profile is used to demonstrate that both the cooperativeness and the change in cooperativeness over evolutionary time are substantially different for different resource levels within a representational type. Lookup tables and neural nets are found to change the least when the resource levels they are presented with are varied, while Markov chains vary the most. Available internal resources are also found to change the competitive ability of agents as well as the rate at which they become cooperative as evolution proceeds.

Application of ODT to constant volume autoignition problems

AbstractThe One‐Dimensional Turbulence (ODT) model is applied to a constant volume configuration by means of a periodic, one‐dimensional domain subject to randomized ensemble members with initial inhomogeneous temperature fields and homogeneous mass fraction profiles. The multidimensional turbulent interactions in the flow are modeled by the separate implementation of turbulent advection and the diffusion‐reaction processes, neglecting the mean advection of the system. On one hand, turbulent advection is modeled by means of the eddy events defined within the framework of ODT; on the other hand, the diffusion‐reaction system is solved by means of the Zero‐Mach limit conservation equations discretized with a 1D Finite Volume Method (FVM). The treatment is specialized in this work to constant volume systems. Due to the inherent stiffness of the diffusion‐reaction system, an operator splitting approach is also included in the formulation. Results for n‐Heptane chemistry comprising the temporal evolution of the heat release rate, pressure and normalized density‐weighted displacement speed are shown and compared to DNS results from Yoo et al. [Combust. Flame 158 (2011) 1727‐1741], in terms of individual ensemble members and mean ensemble behavior. The results show that it is possible to obtain reasonably good results in comparison to the DNS if an appropriate set of initial conditions is used. Furthermore, it is shown that the model uncertainty is negligible in comparison to the ensemble standard deviation introduced by randomized initial conditions. Overall, this work introduces the framework for constant volume autoignition in ODT and shows its efficiency for complex chemistry simulations. (© 2017 Wiley‐VCH Verlag GmbH & Co. KGaA, Weinheim)

Bright x-rays reveal shifting deformation states and effects of the microstructure on the plastic deformation of crystalline materials

The plastic deformation of crystalline materials is usually modeled as smoothly progressing in space and time, yet modern studies show intermittency in the deformation dynamics of single-crystals arising from avalanche behavior of dislocation ensembles under uniform applied loads. However, once the prism of the microstructure in polycrystalline materials disperses and redistributes the load on a grain-by-grain basis, additional length and time scales are involved. Thus, the question is open as to how deformation intermittency manifests for the nonuniform grain-scale internal driving forces interacting with the finer-scale dislocation ensemble behavior. In this work we track the evolution of elastic strain within individual grains of a creep-loaded titanium alloy, revealing widely varying internal strains that fluctuate over time. The findings provide direct evidence of how flow intermittency proceeds for an aggregate of $\ensuremath{\sim}700$ grains while showing the influences of multiscale ensemble interactions and opening new avenues for advancing plasticity modeling.

Thermodynamic framework for information in nanoscale systems with memory

Information is represented by linear strings of symbols with memory that carry errors as a result of their stochastic nature. Proofreading and edition are assumed to improve certainty although such processes may not be effective. Here, we develop a thermodynamic theory for material chains made up of nanoscopic subunits with symbolic meaning in the presence of memory. This framework is based on the characterization of single sequences of symbols constructed under a protocol and is used to derive the behavior of ensembles of sequences similarly constructed. We then analyze the role of proofreading and edition in the presence of memory finding conditions to make revision an effective process, namely, to decrease the entropy of the chain. Finally, we apply our formalism to DNA replication and RNA transcription finding that Watson and Crick hybridization energies with which nucleotides are branched to the template strand during the copying process are optimal to regulate the fidelity in proofreading. These results are important in applications of information theory to a variety of solid-state physical systems and other biomolecular processes.

Global Spectrum Fluctuations for Gaussian Beta Ensembles: A Martingale Approach

The paper describes the global limiting behavior of Gaussian beta ensembles where the parameter $$\beta $$ is allowed to vary with the matrix size n. In particular, we show that as $$n \rightarrow \infty $$ with $$n\beta \rightarrow \infty $$ , the empirical distribution converges weakly to the semicircle distribution, almost surely. The Gaussian fluctuation around the limit is then derived by a martingale approach.

Finite-size effects in a stochastic Kuramoto model

We present a collective coordinate approach to study the collective behaviour of a finite ensemble of N stochastic Kuramoto oscillators using two degrees of freedom: one describing the shape dynamics of the oscillators and one describing their mean phase. Contrary to the thermodynamic limit N → ∞ in which the mean phase of the cluster of globally synchronized oscillators is constant in time, the mean phase of a finite-size cluster experiences Brownian diffusion with a variance proportional to 1/N. This finite-size effect is quantitatively well captured by our collective coordinate approach.

Temperature behavior of the antiferromagnetic susceptibility of nanoferrihydrite from the measurements of the magnetization curves in fields of up to 250 kOe

The cross-breeding problem of the temperature dependence of the antiferromagnetic susceptibility of ferrihydrite nanoparticles is considered. Iron ions Fe3+ in ferrihydrite are ordered antiferromagnetically; however, the existence of defects on the surface and in the bulk of nanoparticles induces a noncompensated magnetic moment that leads to a typical superparamagnetic behavior of ensemble of the nanoparticles with a characteristic blocking temperature. In an unblocked state, magnetization curves of such objects are described as a superposition of the Langevin function and the linear-in-field contribution of the antiferromagnetic “core” of the nanoparticles. According to many studies of the magnetization curves performed on ferrihydrite (and related ferritin) nanoparticles in fields to 60 kOe, dependence χAF(T) decreases as temperature increases, which was related before to the superantiferromagnetism effect. As the magnetic field range increases to 250 kOe, the values of χAF obtained from an analysis of the magnetization curves become lower in magnitude; however, the character of the temperature evolution of χAF is changed: now, dependence χAF(T) is an increasing function. The latter is typical for a system of AF particles with random orientation of the crystallographic axes. To correctly determine the antiferromagnetic susceptibility of AF nanoparticles (at least, ferrihydrite) and to search for effects related to the superantiferromagnetism effect, it is necessary to use in experiments the range of magnetic field significantly higher than that the standard value 60 kOe used in most experiments. The study of the temperature evolution of the magnetization curves shows that the observed crossover is due to the existence of small magnetic moments in the samples.

Potassium (De-)insertion Processes in Prussian Blue Particles: Ensemble versus Single Nanoparticle Behaviour.

Potassium (de-)insertion from Prussian blue (PB) is investigated at the single and multi-particle scale. The electrochemical behaviour is found to differ between the two measurement types. At the single particle level, oxidation of the PB nanoparticles with concomitant K+ deinsertion occurs more readily than the associated reduction, relating to K+ insertion. In contrast, the cyclic voltammetry of PB in a composite electrode containing conductive additives and polymeric binder suggests the opposite behaviour. Implications for assessing battery materials are discussed.

Hysteresis of MnFePSi Spherical Powder Ensembles Studied by Magneto‐Optical Imaging

Temperature‐dependent magneto‐optical imaging is applied to study the thermal hysteresis of magnetocaloric MnFePSi spherical powder‐packed beds across their magneto‐elastic transition. Cooling and heating imaging series are used to analyze the transition of such a complex powder ensemble. The magnetization versus temperature behavior reconstructed from these local measurements shows very good agreement with integral measurements of the magnetization of the whole packed bed. Hence, local magneto‐optical imaging measurements represent the ensemble behavior well if the number of measurements is large enough. Furthermore, we analyzed the Curie temperature (TC) distribution of layers with different TC values and observed that the spread of TC within one layer is larger than the spacing between different layers, leading to a gradual switching behavior of the layer ensemble. Additionally, high resolution light microscopy was applied to observe the transition of individual particles, and correlate it to the local magnetic measurements.

Experimental observation of blood erythrocyte structure in the field of standing surface acoustic waves

The paper presents experimental results of observing the structurization effect for one of the formed elements of blood—erythrocytes—in the field of standing surface acoustic waves. Characteristic images of the striated structures formed by erythrocytes on the surface of lithium niobate as result of ultrasound action have been obtained. The results on the ultrasound structurization of erythrocytes in a blood sample and of calcium carbonate particles in an aqueous colloid solution have been comparatively analyzed. It has been noted that the achieved effect agrees qualitatively with the theoretical model of the behavior of colloid particle ensembles in an acoustic field developed by O.V. Rudenko et al.

Experimental Studies of the Capacitive-Potential Relationship for Ionic Liquid – Electrode Interfaces

The electrochemical double layer (EDL) in ionic liquid (IL) solvents plays an important role in myriad energy storage and conversion applications. A clear description of molecular organization within this interfacial region requires a multipronged approach. This presentation will discuss studies of the IL – electrode interface using AC voltammetry, electrochemical impedance spectroscopy (EIS), and vibrational spectroscopy covering slow (re)orientation / movement of ILs within the EDL as it relates to capacitive hysteresis, and make critical comparisons of capacitance vs. potential relationships to theoretical predictions. ILs at an electrified interface have been shown to exhibit capacitive hysteresis depending on the applied potential scan direction (e.g. cathodic or anodic), the extent of which depends on electrode surface material and the measurement technique employed.1-3 Recent work in our group examined several aprotic and protic ILs on metallic, carbon, and semiconducting electrodes demonstrating that capacitive hysteresis is not necessarily a uniform feature of the IL electrified interface. Our studies use large amplitude Fourier transformed alternating current (FT-AC) voltammetry, which demonstrates little (<10 %) hysteresis in the resulting capacitance vs. potential curve respective to the electrochemical potential scan direction. This highlights the benefits of utilizing large amplitude FT-AC voltammetry to probe capacitive currents in ILs. Additional work employs vibrational spectroscopy to study the evolution of the IL EDL under an applied potential. This data provides a vantage point to discuss capacitive hysteresis and how it could relate to molecular (re)orientation in ILs. Our preliminary data show that the IL vibrational profile shows small changes when responding to a potential step of 2 V within the EDL potential window. However, the vibrational profile exhibits noticeable hysteresis in IR peak intensities when undergoing positive- and negative-going applied potential scan directions further demonstrating the slow response times in ILs. It has been suggested that slow (re)orientation of ILs within the EDL could be the mechanism behind the observed hysteresis and that these processes are likely a common feature of the IL – electrode interface.4-5 Depending on the electrochemical technique employed the effective ‘scan rate’ can vary from less than one minute (e.g. FT-AC voltammetry) to several hours (e.g. EIS) when acquiring capacitance data over a range of potentials. Our work using broadband EIS to study the 1-ethyl-3-methylimidazolium tris(pentafluoroethyl)-trifluorophosphate – polycrystalline gold interface demonstrates over a 2 V window that capacitive hysteresis is absent based on several potential scan directions employed compared to Au(111) which exhibits this phenomenon.1 Further this work spanning from 1 MHz to 0.01 Hz suggests the slow process (visible in the complex capacitance plane plot as an arc in the low frequency region) is also absent on the polycrystalline gold electrode compared to the Au(111) single-crystal surface.1 Our work with large amplitude FT-AC voltammetry suggests three possible scenarios to explain contradictions with previous reports: (1) large amplitude FT-AC voltammetry scans the potential window cycle fast enough (~100 mV s-1) relative to slow movement of IL EDL ions to not capture any hysteresis processes, (2) the large perturbation amplitude employed overcomes the energetic barrier for interfacial IL ion movement to exhibit hysteresis processes or (3) capacitive hysteresis and slow (re)orientation are not necessarily common features of the IL – electrode interface. Capacitance curvature in published scientific literature show a wide range of results, even for similar electrochemical systems. Additionally, it has proved challenging to unite theoretical predictions with experimental observations for IL capacitance responses. ILs are concentrated in the sense that they contain no molecular solvent and one viewpoint is they are composed entirely of dissociated ions. However, recent reports challenge this view to suggest they are not well dissociated and behave as dilute electrolytes. Our work examining the 1-butyl-3-methylimidazolum tetrafluoroborate – polycrystalline gold interface corroborates the latter viewpoint. Furthermore, our studies of the IL – semiconductor electrode interface demonstrate a capacitance response analogous to dilute aqueous electrolytes at a semiconductor electrode. Specifically, we report relatively featureless, ‘rising’ capacitance curvature that shows minimal dependence on the nature of the IL (i.e. protic vs. aprotic). Capacitance-potential curvature suggests at the ensemble behavior of the EDL but coupling potential control with spectroscopy can provide a powerful method of probing interfacial chemistry. It is anticipated that this presentation will bring to light some basic questions of IL behavior at an electrified interface.

The Role of Forcings in the Twentieth-Century North Atlantic Multidecadal Variability: The 1940–75 North Atlantic Cooling Case Study

Abstract Results from a study inspecting the origins of multidecadal variability in the North Atlantic sea surface temperature (NASST) are presented. The authors target in particular the 1940–75 “warm-to-cold” transition, an event that is generally framed in the context of the longer-term Atlantic multidecadal variability (AMV) cycle, in turn associated with the Atlantic meridional overturning circulation (AMOC) internal variability. Here the authors examine the ability of uninitialized, historical integrations from the phase 5 of the Coupled Model Intercomparison Project (CMIP5) archive to retrospectively reproduce this specific episode of twentieth-century climatic history, under a hierarchy of forcing conditions. For this purpose, both standard and so-called historical Misc CMIP5 simulations of the historical climate (combining selected natural and anthropogenic forcings) are exploited. Based on this multimodel analysis, evidence is found for a significant influence of anthropogenic agents on multidecadal sea surface temperature (SST) fluctuations across the Atlantic sector, suggesting that anthropogenic aerosols and greenhouse gases might have played a key role in the 1940–75 North Atlantic cooling. However, the diagnosed forced response in CMIP5 models appears to be affected by a large uncertainty, with only a limited subset of models displaying significant skill in reproducing the mid-twentieth-century NASST cooling. Such uncertainty originates from the existence of well-defined behavioral clusters within the analyzed CMIP5 ensembles, with the bulk of the models splitting into two main clusters. Such a strong polarization calls for some caution when using a multimodel ensemble mean in climate model analyses, as averaging across fairly distinct model populations may result, through mutual cancellation, in a rather artificial description of the actual multimodel ensemble behavior. A potentially important role for both anthropogenic aerosols and greenhouse gases with regard to the observed North Atlantic multidecadal variability has clear implications for decadal predictability and predictions. The uncertainty associated with alternative aerosol and greenhouse gas emission scenarios should be duly accounted for in designing a common protocol for coordinated decadal forecast experiments.

Small teams of myosin Vc motors coordinate their stepping for efficient cargo transport on actin bundles

Myosin Vc (myoVc) is unique among vertebrate class V myosin isoforms in that it requires teams of motors to move continuously on single actin filaments. Single molecules of myoVc cannot take multiple hand-over-hand steps from one actin-binding site to the next without dissociating, in stark contrast to the well studied myosin Va (myoVa) isoform. At low salt, single myoVc motors can, however, move processively on actin bundles, and at physiologic ionic strength, even teams of myoVc motors require actin bundles to sustain continuous motion. Here, we linked defined numbers of myoVc or myoVa molecules to DNA nanostructures as synthetic cargos. Using total internal reflectance fluorescence microscopy, we compared the stepping behavior of myoVc versus myoVa ensembles and myoVc stepping patterns on single actin filaments versus actin bundles. Run lengths of both myoVc and myoVa teams increased with motor number, but only multiple myoVc motors showed a run-length enhancement on actin bundles compared with actin filaments. By resolving the stepping behavior of individual myoVc motors with a quantum dot bound to the motor domain, we found that coupling of two myoVc motors significantly decreased the futile back and side steps that were frequently observed for single myoVc motors. Changes in the inter-motor distance between two coupled myoVc motors affected stepping dynamics, suggesting that mechanical tension coordinates the stepping behavior of two myoVc motors for efficient directional motion. Our study provides a molecular basis to explain how teams of myoVc motors are suited to transport cargos such as zymogen granules on actin bundles.