Molecular Dynamics Simulation of Self Diffusion in Microclusters

Abstract

Molecular dynamics simulation is carried out to study the mechanism of self diffusion which is characteristic of solid-like microclusters. A two-dimensional system with the Lennard-Jones potential is employed and the temperatures near the triple point of the two-dimensional bulk system are adopted for the simulation. The results show that: a) microclusters consist of two regions, i.e., solid-like cores and liquid-like surface regions, b) the size dependence of the diffusion coefficient for microclusters is weak, and the value of the solid-like core region is not much different from that of the bulk liquid, c) the activation energy of diffusion for microclusters is twenty to thirty times larger than that for the bulk liquid, d) the diffusion mechanism in the solid-like region involves the collective motion of small domains containing ten to twenty atoms which results in the formation of low density regions, sometimes even vacancy clusters, between them, and atoms in the low density regions change their positions to cause diffusion.     

Mechanisms of Left-Right Coordination in Mammalian Locomotor Pattern Generation Circuits: A Mathematical Modeling View

The locomotor gait in limbed animals is defined by the left-right leg coordination and locomotor speed. Coordination between left and right neural activities in the spinal cord controlling left and right legs is provided by commissural interneurons (CINs). Several CIN types have been genetically identified, including the excitatory V3 and excitatory and inhibitory V0 types. Recent studies demonstrated that genetic elimination of all V0 CINs caused switching from a normal left-right alternating activity to a left-right synchronized “hopping” pattern. Furthermore, ablation of only the inhibitory V0 CINs (V0_D subtype) resulted in a lack of left-right alternation at low locomotor frequencies and retaining this alternation at high frequencies, whereas selective ablation of the excitatory V0 neurons (V0_V subtype) maintained the left–right alternation at low frequencies and switched to a hopping pattern at high frequencies. To analyze these findings, we developed a simplified mathematical model of neural circuits consisting of four pacemaker neurons representing left and right, flexor and extensor rhythm-generating centers interacting via commissural pathways representing V3, V0_D, and V0_V CINs. The locomotor frequency was controlled by a parameter defining the excitation of neurons and commissural pathways mimicking the effects of N-methyl-D-aspartate on locomotor frequency in isolated rodent spinal cord preparations. The model demonstrated a typical left-right alternating pattern under control conditions, switching to a hopping activity at any frequency after removing both V0 connections, a synchronized pattern at low frequencies with alternation at high frequencies after removing only V0_D connections, and an alternating pattern at low frequencies with hopping at high frequencies after removing only V0_V connections. We used bifurcation theory and fast-slow decomposition methods to analyze network behavior in the above regimes and transitions between them. The model reproduced, and suggested explanation for, a series of experimental phenomena and generated predictions available for experimental testing.     

Transition to quorum sensing in an Agrobacterium population: A stochastic model

Understanding of the intracellular molecular machinery that is responsible for the complex collective behavior of multicellular populations is an exigent problem of modern biology. Quorum sensing, which allows bacteria to activate genetic programs cooperatively, provides an instructive and tractable example illuminating the causal relationships between the molecular organization of gene networks and the complex phenotypes they control. In this work we—to our knowledge for the first time—present a detailed model of the population-wide transition to quorum sensing using the example of Agrobacterium tumefaciens. We construct a model describing the Ti plasmid quorum-sensing gene network and demonstrate that it behaves as an “on–off” gene expression switch that is robust to molecular noise and that activates the plasmid conjugation program in response to the increase in autoinducer concentration. This intracellular model is then incorporated into an agent-based stochastic population model that also describes bacterial motion, cell division, and chemical communication. Simulating the transition to quorum sensing in a liquid medium and biofilm, we explain the experimentally observed gradual manifestation of the quorum-sensing phenotype by showing that the transition of individual model cells into the “on” state is spread stochastically over a broad range of autoinducer concentrations. At the same time, the population-averaged values of critical autoinducer concentration and the threshold population density are shown to be robust to variability between individual cells, predictable and specific to particular growth conditions. Our modeling approach connects intracellular and population scales of the quorum-sensing phenomenon and provides plausible answers to the long-standing questions regarding the ecological and evolutionary significance of the phenomenon. Thus, we demonstrate that the transition to quorum sensing requires a much higher threshold cell density in liquid medium than in biofilm, and on this basis we hypothesize that in Agrobacterium quorum sensing serves as the detector of biofilm formation.     

Weighting of Spatial and Spectro-Temporal Cues for Auditory Scene Analysis by Human Listeners

The auditory system creates a neuronal representation of the acoustic world based on spectral and temporal cues present at the listener''s ears, including cues that potentially signal the locations of sounds. Discrimination of concurrent sounds from multiple sources is especially challenging. The current study is part of an effort to better understand the neuronal mechanisms governing this process, which has been termed “auditory scene analysis”. In particular, we are interested in spatial release from masking by which spatial cues can segregate signals from other competing sounds, thereby overcoming the tendency of overlapping spectra and/or common temporal envelopes to fuse signals with maskers. We studied detection of pulsed tones in free-field conditions in the presence of concurrent multi-tone non-speech maskers. In “energetic” masking conditions, in which the frequencies of maskers fell within the ±1/3-octave band containing the signal, spatial release from masking at low frequencies (∼600 Hz) was found to be about 10 dB. In contrast, negligible spatial release from energetic masking was seen at high frequencies (∼4000 Hz). We observed robust spatial release from masking in broadband “informational” masking conditions, in which listeners could confuse signal with masker even though there was no spectral overlap. Substantial spatial release was observed in conditions in which the onsets of the signal and all masker components were synchronized, and spatial release was even greater under asynchronous conditions. Spatial cues limited to high frequencies (>1500 Hz), which could have included interaural level differences and the better-ear effect, produced only limited improvement in signal detection. Substantially greater improvement was seen for low-frequency sounds, for which interaural time differences are the dominant spatial cue.     

Molecular Dynamics Simulation of Collective Motions in Binary Liquids

Collective dynamic properties of different kind of binary liquid mixtures have been investigated by molecular dynamics simulation. The study includes both the longitudinal and the transverse current spectra in simple liquid alloys, 1:1 molten salts and liquid binary mixtures of neutral particles with an ionic-like structure. These systems were chosen as representative of binary liquids with different static structures in order to analyse the effects of structural ordering on the mechanisms of dynamic collective properties. The effect of the mass asymmetry between the two species in the mixture has been also discussed from the results for two different mass ratios for each kind of structure. Two length scales have been considered. On the one hand, the hydrodynamic scale (low wave numbers), where the modes for the partial currents of the two species are characterised by very close frequencies. On the other hand, the molecular scale (higher wave numbers), where the characteristic frequencies for the two species show noticeable differences. Vibrational concentration current modes (optic modes) have been found in neutral mixtures though their influence is rather weak, being the collective dynamic properties of this kind of systems dominated by the mass current modes (acoustic modes). On the contrary, in mixtures of charged particles such as molten salts the contribution of the concentration (charge) currents to the collective dynamics is important and optic modes can be characterised by a well-defined frequency for a wide range of wave numbers. It has been observed that heavy particles have a more relevant role on the mass current correlations whereas light particles play a dominant role on the concentration current correlations. The overall results for the three kinds of liquid mixtures analysed in this paper show that both the longitudinal and transverse current spectra are little dependent on the static structure of the system whereas marked differences are revealed when the particles in the system are either neutral or carry an electric charge.     

Time-Lapse Photography of Bacillus subtilis L-Forms Replicating in Liquid Medium

Phase-contrast observations indicate that an L-form of Bacillus subtilis divides in liquid medium by a “budding-like” mechanism without participation of “large bodies” or “elementary bodies.”     

Liquid Chromatographic-Fluorescence Determination of Ammonia from Nitrogenase Reactions: A 2-Min Assay

The analytical potential of the reaction of ammonia with o-phthalaldehyde mercaptoethanol reagent at pH 7 (an atypical fluorescence) has already been demonstrated. This, coupled with additional findings reported here, has led to an ammonia determination well suited to nitrogenase studies. As a result, large numbers of samples can be rapidly analyzed by high-pressure liquid chromatrography methods under mild conditions and without prior microdiffusion. Neither sodium dithionite (or other components of the usual nitrogenase assay), nor alternative substrates (cyanide, azide, methyl isonitrile), nor their products (methylamine, dimethylamine, hydrazine) interfere. High-pressure liquid chromatography showed that the fluorescent “product” of the o-phthalaldehyde mercaptoethanol reagent-ammonia reaction was, in fact, more than just a single compound. Despite this, once the proper solvent composition was found, high-pressure liquid chromatography with a small inexpensive C₁₈ “guard” column proved quite fast and reproducible for this measurement. Fluorescence response to ammonia was linear to at least 40 nmol/ml. A previous problem, long-term stability of the fluorescence, was solved by running the reactions in the dark. Background ammonia in the buffer could be substantially reduced by an analogous o-phthalaldehyde mercaptoethanol reagent reaction, using t-butyl mercaptan, and solvent extraction.     

Effect of cellular rearrangement time delays on the rheology of vertex models for confluent tissues

Large-scale tissue deformation during biological processes such as morphogenesis requires cellular rearrangements. The simplest rearrangement in confluent cellular monolayers involves neighbor exchanges among four cells, called a T1 transition, in analogy to foams. But unlike foams, cells must execute a sequence of molecular processes, such as endocytosis of adhesion molecules, to complete a T1 transition. Such processes could take a long time compared to other timescales in the tissue. In this work, we incorporate this idea by augmenting vertex models to require a fixed, finite time for T1 transitions, which we call the “T1 delay time”. We study how variations in T1 delay time affect tissue mechanics, by quantifying the relaxation time of tissues in the presence of T1 delays and comparing that to the cell-shape based timescale that characterizes fluidity in the absence of any T1 delays. We show that the molecular-scale T1 delay timescale dominates over the cell shape-scale collective response timescale when the T1 delay time is the larger of the two. We extend this analysis to tissues that become anisotropic under convergent extension, finding similar results. Moreover, we find that increasing the T1 delay time increases the percentage of higher-fold coordinated vertices and rosettes, and decreases the overall number of successful T1s, contributing to a more elastic-like—and less fluid-like—tissue response. Our work suggests that molecular mechanisms that act as a brake on T1 transitions could stiffen global tissue mechanics and enhance rosette formation during morphogenesis.     

Reading the Mind in the Eyes or Reading between the Lines? Theory of Mind Predicts Collective Intelligence Equally Well Online and Face-To-Face

Recent research with face-to-face groups found that a measure of general group effectiveness (called “collective intelligence”) predicted a group’s performance on a wide range of different tasks. The same research also found that collective intelligence was correlated with the individual group members’ ability to reason about the mental states of others (an ability called “Theory of Mind” or “ToM”). Since ToM was measured in this work by a test that requires participants to “read” the mental states of others from looking at their eyes (the “Reading the Mind in the Eyes” test), it is uncertain whether the same results would emerge in online groups where these visual cues are not available. Here we find that: (1) a collective intelligence factor characterizes group performance approximately as well for online groups as for face-to-face groups; and (2) surprisingly, the ToM measure is equally predictive of collective intelligence in both face-to-face and online groups, even though the online groups communicate only via text and never see each other at all. This provides strong evidence that ToM abilities are just as important to group performance in online environments with limited nonverbal cues as they are face-to-face. It also suggests that the Reading the Mind in the Eyes test measures a deeper, domain-independent aspect of social reasoning, not merely the ability to recognize facial expressions of mental states.     

Comparison of Bacterial Lipopolysaccharides by High-Performance Liquid Chromatography

A comparison of lipid-free polysaccharides from gram-negative bacteria was rapidly accomplished by using high-performance liquid chromatography of underivatized hydrolysates. Examination of a number of such products revealed that, contrary to earlier reports, Xanthomonas campestris lipopolysaccharide contained heptose, together with rhamnose and galactose, but not mannose. The polymers from the methanotrophs “Methylomonas albus” and “Methylosinus trichosporium” contained heptose and glucose, and that from a “Klebsiella aerogenes” strain contained heptose, glucose, and galactose. The absence of heptose from the lipopolysaccharide of Myxococcus xanthus was confirmed.     

Tracheal motile cilia in mice require CAMSAP3 for the formation of central microtubule pair and coordinated beating

Motile cilia of multiciliated epithelial cells undergo synchronized beating to produce fluid flow along the luminal surface of various organs. Each motile cilium consists of an axoneme and a basal body (BB), which are linked by a “transition zone” (TZ). The axoneme exhibits a characteristic 9+2 microtubule arrangement important for ciliary motion, but how this microtubule system is generated is not yet fully understood. Here we show that calmodulin-regulated spectrin-associated protein 3 (CAMSAP3), a protein that can stabilize the minus-end of a microtubule, concentrates at multiple sites of the cilium–BB complex, including the upper region of the TZ or the axonemal basal plate (BP) where the central pair of microtubules (CP) initiates. CAMSAP3 dysfunction resulted in loss of the CP and partial distortion of the BP, as well as the failure of multicilia to undergo synchronized beating. These findings suggest that CAMSAP3 plays pivotal roles in the formation or stabilization of the CP by localizing at the basal region of the axoneme and thereby supports the coordinated motion of multicilia in airway epithelial cells.     

A new method for measuring the yield stress in thin layers of sedimenting blood.

A new method is presented to describe the low shear rate behavior of blood. We observed the response of a thin layer of sedimenting blood to a graded shear stress in a wedge-shaped chamber. The method allows quantitation of the degree of phase separation between red cells and plasma, and extracts the yield stress of the cell phase as a function of hematocrit. Our studies showed that the behavior of normal human blood underwent a transition from a solid-like gel to a Casson fluid. This transition began at the Casson predicted yield stress. The viscoelastic properties of blood were examined at shear stresses below the yield stress. The measured Young's elastic moduli were in good agreement with published data. The yield stress of blood showed a linear dependence on hematocrit up to 60%, and increased more rapidly at higher hematocrit.     

Collective predator evasion: Putting the criticality hypothesis to the test

According to the criticality hypothesis, collective biological systems should operate in a special parameter region, close to so-called critical points, where the collective behavior undergoes a qualitative change between different dynamical regimes. Critical systems exhibit unique properties, which may benefit collective information processing such as maximal responsiveness to external stimuli. Besides neuronal and gene-regulatory networks, recent empirical data suggests that also animal collectives may be examples of self-organized critical systems. However, open questions about self-organization mechanisms in animal groups remain: Evolutionary adaptation towards a group-level optimum (group-level selection), implicitly assumed in the “criticality hypothesis”, appears in general not reasonable for fission-fusion groups composed of non-related individuals. Furthermore, previous theoretical work relies on non-spatial models, which ignore potentially important self-organization and spatial sorting effects. Using a generic, spatially-explicit model of schooling prey being attacked by a predator, we show first that schools operating at criticality perform best. However, this is not due to optimal response of the prey to the predator, as suggested by the “criticality hypothesis”, but rather due to the spatial structure of the prey school at criticality. Secondly, by investigating individual-level evolution, we show that strong spatial self-sorting effects at the critical point lead to strong selection gradients, and make it an evolutionary unstable state. Our results demonstrate the decisive role of spatio-temporal phenomena in collective behavior, and that individual-level selection is in general not a viable mechanism for self-tuning of unrelated animal groups towards criticality.     

Diffusing wave spectroscopy microrheology of actin filament networks.

Filamentous actin (F-actin), one of the constituents of the cytoskeleton, is believed to be the most important participant in the motion and mechanical integrity of eukaryotic cells. Traditionally, the viscoelastic moduli of F-actin networks have been measured by imposing a small mechanical strain and quantifying the resulting stress. The magnitude of the viscoelastic moduli, their concentration dependence and strain dependence, as well as the viscoelastic nature (solid-like or liquid-like) of networks of uncross-linked F-actin, have been the subjects of debate. Although this paper helps to resolve the debate and establishes the extent of the linear regime of F-actin networks' rheology, we report novel measurements of the high-frequency behavior of networks of F-actin, using a noninvasive light-scattering based technique, diffusing wave spectroscopy (DWS). Because no external strain is applied, our optical assay generates measurements of the mechanical properties of F-actin networks that avoid many ambiguities inherent in mechanical measurements. We observe that the elastic modulus has a small magnitude, no strain dependence, and a weak concentration dependence. Therefore, F-actin alone is not sufficient to generate the elastic modulus necessary to sustain the structural rigidity of most cells or support new cellular protrusions. Unlike previous studies, our measurements show that the mechanical properties of F-actin are highly dependent on the frequency content of the deformation. We show that the loss modulus unexpectedly dominates the elastic modulus at high frequencies, which are key for fast transitions. Finally, the measured mean square displacement of the optical probes, which is also generated by DWS measurements, offers new insight into the local bending fluctuations of the individual actin filaments and shows how they generate enhanced dissipation at short time scales.     

Challenges and dreams: physics of weak interactions essential to life

Biological systems display stunning capacities to self-organize. Moreover, their subcellular architectures are dynamic and responsive to changing needs and conditions. Key to these properties are manifold weak “quinary” interactions that have evolved to create specific spatial networks of macromolecules. These specific arrangements of molecules enable signals to be propagated over distances much greater than molecular dimensions, create phase separations that define functional regions in cells, and amplify cellular responses to changes in their environments. A major challenge is to develop biochemical tools and physical models to describe the panoply of weak interactions operating in cells. We also need better approaches to measure the biases in the spatial distributions of cellular macromolecules that result from the integrated action of multiple weak interactions. Partnerships between cell biologists, biochemists, and physicists are required to deploy these methods. Together these approaches will help us realize the dream of understanding the biological “glue” that sustains life at a molecular and cellular level.     

Darwin's Manufactory Hypothesis Is Confirmed and Predicts the Extinction Risk of Extant Birds

In the Origin of Species Darwin hypothesized that the “manufactory” of species operates at different rates in different lineages and that the richness of taxonomic units is autocorrelated across levels of the taxonomic hierarchy. We confirm the manufactory hypothesis using a database of all the world''s extant avian subspecies, species and genera. The hypothesis is confirmed both in correlations across all genera and in paired comparisons controlling for phylogeny. We also find that the modern risk of extinction, as measured by “Red List” classifications, differs across the different categories of genera identified by Darwin. Specifically, species in “manufactory” genera are less likely to be threatened, endangered or recently extinct than are “weak manufactory” genera. Therefore, although Darwin used his hypothesis to investigate past evolutionary processes, we find that the hypothesis also foreshadows future changes to the evolutionary tree.     

Disturbance and predation risk influence vigilance synchrony of black‐necked cranes Grus nigricollis,but not as strongly as expected

Animals monitor surrounding dangers independently or cooperatively (synchronized and coordinated vigilance), with independent and synchronized scanning being prevalent. Coordinated vigilance, including unique sentinel behavior, is rare in nature, since it is time‐consuming and limited in terms of benefits. No evidence showed animals adopt alternative vigilance strategies during antipredation scanning yet. Considering the nonindependent nature of both synchronization and coordination, we assessed whether group members could keep alert synchronously or in a coordinated fashion under different circumstance. We studied how human behavior and species‐specific variables impacted individual and collective vigilance of globally threatened black‐necked cranes (Grus nigricollis) and explored behavior‐based wildlife management. We tested both predation risk (number of juveniles in group) and human disturbance (level and distance) effects on individual and collective antipredation vigilance of black‐necked crane families. Adults spent significantly more time (proportion and duration) on scanning than juveniles, and parents with juveniles behaved more vigilant. Both adults and juveniles increased time allocation and duration on vigilance with observer proximity. Deviation between observed and expected collective vigilance varied with disturbance and predation risk from zero, but not significantly so, indicating that an independent vigilance strategy was adopted by black‐necked crane couples. The birds showed synchronized vigilance in low disturbance areas, with fewer juveniles and far from observers; otherwise, they scanned in coordinated fashion. The collective vigilance, from synchronized to coordinated pattern, varied as a function of observer distance that helped us determine a safe distance of 403.75 m for the most vulnerable family groups with two juveniles. We argue that vigilance could constitute a prime indicator in behavior‐based species conservation, and we suggesting a safe distance of at least 400 m should be considered in future tourist management.     

Beyond arbitrium: identification of a second communication system in Bacillus phage phi3T that may regulate host defense mechanisms

The evolutionary stability of temperate bacteriophages at low abundance of susceptible bacterial hosts lies in the trade-off between the maximization of phage replication, performed by the host-destructive lytic cycle, and the protection of the phage-host collective, enacted by lysogeny. Upon Bacillus infection, Bacillus phages phi3T rely on the “arbitrium” quorum sensing (QS) system to communicate on their population density in order to orchestrate the lysis-to-lysogeny transition. At high phage densities, where there may be limited host cells to infect, lysogeny is induced to preserve chances of phage survival. Here, we report the presence of an additional, host-derived QS system in the phi3T genome, making it the first known virus with two communication systems. Specifically, this additional system, coined “Rapφ-Phrφ”, is predicted to downregulate host defense mechanisms during the viral infection, but only upon stress or high abundance of Bacillus cells and at low density of population of the phi3T phages. Post-lysogenization, Rapφ-Phrφ is also predicted to provide the lysogenized bacteria with an immediate fitness advantage: delaying the costly production of public goods while nonetheless benefiting from the public goods produced by other non-lysogenized Bacillus bacteria. The discovered “Rapφ-Phrφ” QS system hence provides novel mechanistic insights into how phage communication systems could contribute to the phage-host evolutionary stability.Subject terms: Bacteriophages, Viral genetics     

DNA length tunes the fluidity of DNA-based condensates

Living organisms typically store their genomic DNA in a condensed form. Mechanistically, DNA condensation can be driven by macromolecular crowding, multivalent cations, or positively charged proteins. At low DNA concentration, condensation triggers the conformational change of individual DNA molecules into a compacted state, with distinct morphologies. Above a critical DNA concentration, condensation goes along with phase separation into a DNA-dilute and a DNA-dense phase. The latter DNA-dense phase can have different material properties and has been reported to be rather liquid-like or solid-like depending on the characteristics of the DNA and the solvent composition. Here, we systematically assess the influence of DNA length on the properties of the resulting condensates. We show that short DNA molecules with sizes below 1 kb can form dynamic liquid-like assemblies when condensation is triggered by polyethylene glycol and magnesium ions, binding of linker histone H1, or nucleosome reconstitution in combination with linker histone H1. With increasing DNA length, molecules preferentially condense into less dynamic more solid-like assemblies, with phage λ-DNA with 48.5 kb forming mostly solid-like assemblies under the conditions assessed here. The transition from liquid-like to solid-like condensates appears to be gradual, with DNA molecules of roughly 1–10 kb forming condensates with intermediate properties. Titration experiments with linker histone H1 suggest that the fluidity of condensates depends on the net number of attractive interactions established by each DNA molecule. We conclude that DNA molecules that are much shorter than a typical human gene are able to undergo liquid-liquid phase separation, whereas longer DNA molecules phase separate by default into rather solid-like condensates. We speculate that the local distribution of condensing factors can modulate the effective length of chromosomal domains in the cell. We anticipate that the link between DNA length and fluidity established here will improve our understanding of biomolecular condensates involving DNA.