Molecular Dynamics Simulation of a Feather-Boa Model of a Bacterial Chromosome.

The chromosome of a bacterium consists of a mega-base pair-long circular DNA, which self-organizes within the micron-sized bacterial cell volume, compacting itself by three orders of magnitude. Unlike eukaryotic chromosomes, it lacks a nuclear membrane and freely floats in the cytosol confined by the cell membrane. It is believed that strong confinement, cross-linking by associated proteins, and molecular crowding all contribute to determine chromosome size and morphology. Modelling the chromosome simply as a circular polymer decorated with closed side loops in a cylindrical confining volume has been shown to already recapture some of the salient properties observed experimentally. Here we describe how a computer simulation can be set up to study structure and dynamics of bacterial chromosomes using this model.

Inertia and activity: spiral transitions in semi-flexible, self-avoiding polymers.

We consider a two-dimensional, tangentially active, semi-flexible, self-avoiding polymer to find a dynamical re-entrant transition between motile open chains and spinning achiral spirals with increasing activity. Utilizing probability distributions of the turning number, we ascertain the comparative stability of the spiral structure and present a detailed phase diagram within the activity inertia plane. The onset of spiral formation at low activity levels is governed by a torque balance and is independent of inertia. At higher activities, however, inertial effects lead to spiral destabilization, an effect absent in the overdamped limit. We further delineate alterations in size and shape by analyzing the end-to-end distance distribution and the radius of gyration tensor. The Kullback-Leibler divergence from equilibrium distributions exhibits a non-monotonic relationship with activity, reaching a peak at the most compact spirals characterized by the most persistent spinning. As inertia increases, this divergence from equilibrium diminishes.

When an active bath behaves as an equilibrium one.

Active scalar baths consisting of active Brownian particles are characterized by a non-Gaussian velocity distribution, a kinetic temperature, and a diffusion coefficient that scale with the square of the active velocity v_{0}. While these results hold in overdamped active systems, inertial effects lead to normal velocity distributions, with kinetic temperature and diffusion coefficient increasing as ∼v_{0}^{α} with 1<α<2. Remarkably, the late-time diffusivity and mobility decrease with mass. Moreover, we show that the equilibrium Einstein relation is asymptotically recovered with inertia. In summary, the inertial mass restores an equilibriumlike behavior.

F-box protein FBXB-65 regulates anterograde transport of the kinesin-3 motor UNC-104 through a PTM near its cargo-binding PH domain.

Axonal transport in neurons is essential for cargo movement between the cell body and synapses. Caenorhabditis elegans UNC-104 and its homolog KIF1A are kinesin-3 motors that anterogradely transport precursors of synaptic vesicles (pre-SVs) and are degraded at synapses. However, in C. elegans, touch neuron-specific knockdown of the E1 ubiquitin-activating enzyme, uba-1, leads to UNC-104 accumulation at neuronal ends and synapses. Here, we performed an RNAi screen and identified that depletion of fbxb-65, which encodes an F-box protein, leads to UNC-104 accumulation at neuronal distal ends, and alters UNC-104 net anterograde movement and levels of UNC-104 on cargo without changing synaptic UNC-104 levels. Split fluorescence reconstitution showed that UNC-104 and FBXB-65 interact throughout the neuron. Our theoretical model suggests that UNC-104 might exhibit cooperative cargo binding that is regulated by FBXB-65. FBXB-65 regulates an unidentified post-translational modification (PTM) of UNC-104 in a region beside the cargo-binding PH domain. Both fbxb-65 and UNC-104, independently of FBXB-65, regulate axonal pre-SV distribution, transport of pre-SVs at branch points and organismal lifespan. FBXB-65 regulates a PTM of UNC-104 and the number of motors on the cargo surface, which can fine-tune cargo transport to the synapse.

How reciprocity impacts ordering and phase separation in active nematics?

Active nematics undergo spontaneous symmetry breaking and show phase separation instability. Within the prevailing notion that macroscopic properties depend only on symmetries and conservation laws, different microscopic models are used out of convenience. Here, we test this notion carefully by analyzing three different microscopic models of apolar active nematics. They share the same symmetry but differ in implementing reciprocal or non-reciprocal interactions, including a Vicsek-like implementation. We show how such subtle differences in microscopic realization determine if the ordering transition is continuous or first order. Despite the difference in the type of phase transition, all three models exhibit fluctuation-dominated phase separation and quasi-long-range order in the nematic phase.

Cooperation and competition in the collective drive by motor proteins: mean active force, fluctuations, and self-load.

We consider the dynamics of a bio-filament under the collective drive of motor proteins. They are attached irreversibly to a substrate and undergo stochastic attachment-detachment with the filament to produce a directed force on it. We establish the dependence of the mean directed force and force correlations on the parameters describing the individual motor proteins using analytical theory and direct numerical simulations. The effective Langevin description for the filament motion gives mean-squared displacement, asymptotic diffusion constant, and mobility leading to an effective temperature. Finally, we show how competition between motor protein extensions generates a self-load, describable in terms of the effective temperature, affecting the filament motion.

Self-propulsion with speed and orientation fluctuation: Exact computation of moments and dynamical bistabilities in displacement.

We consider the influence of active speed fluctuations on the dynamics of a d-dimensional active Brownian particle performing a persistent stochastic motion. The speed fluctuation brings about a dynamical anisotropy even in the absence of shape anisotropy. We use the Laplace transform of the Fokker-Planck equation to obtain exact expressions for time-dependent dynamical moments. Our results agree with direct numerical simulations and show several dynamical crossovers determined by the activity, persistence, and speed fluctuation. The dynamical anisotropy leads to a subdiffusive scaling in the parallel component of displacement fluctuation at intermediate times. The kurtosis remains positive at short times determined by the speed fluctuation, crossing over to a negative minimum at intermediate times governed by the persistence before vanishing asymptotically. The probability distribution of particle displacement obtained from numerical simulations in two dimensions shows two crossovers between compact and extended trajectories via two bimodal distributions at intervening times. While the speed fluctuation dominates the first crossover, the second crossover is controlled by persistence like in the wormlike chain model of semiflexible polymers.

Pattern formation, localized and running pulsation on active spherical membranes.

Active force generation by an actin-myosin cortex coupled to a cell membrane allows the cell to deform, respond to the environment, and mediate cell motility and division. Several membrane-bound activator proteins move along it and couple to the membrane curvature. Besides, they can act as nucleating sites for the growth of filamentous actin. Actin polymerization can generate a local outward push on the membrane. Inward pull from the contractile actomyosin cortex can propagate along the membrane via actin filaments. We use coupled evolution of fields to perform linear stability analysis and numerical calculations. As activity overcomes the stabilizing factors such as surface tension and bending rigidity, the spherical membrane shows instability towards pattern formation, localized pulsation, and running pulsation between poles. We present our results in terms of phase diagrams and evolutions of the coupled fields. They have relevance for living cells and can be verified in experiments on artificial cell-like constructs.

Two-step melting of the Weeks-Chandler-Anderson system in two dimensions.

We present a detailed numerical simulation study of a two-dimensional system of particles interacting via the Weeks-Chandler-Anderson potential, the repulsive part of the Lennard-Jones potential. With the reduction of density, the system shows a two-step melting: a continuous melting of solid to hexatic phase, followed by a first-order melting of hexatic to liquid. The solid-hexatic melting is consistent with the Berezinskii-Kosterlitz-Thouless-Halperin-Nelson-Young (BKTHNY) scenario and shows dislocation unbinding. The first-order melting of the hexatic to the liquid phase, on the other hand, displays defect-strings formed at the hexatic-liquid interfaces. We present a detailed phase diagram in the density-temperature plane.

A semiflexible polymer in a gliding assay: reentrant transition, role of turnover and activity.

We consider a model of an extensible semiflexible filament moving in two dimensions on a motility assay of motor proteins represented explicitly as active harmonic linkers. Their heads bind stochastically to polymer segments within a capture radius, and extend along the filament in a directed fashion before detaching. Both the extension and detachment rates are load-dependent and generate an active drive on the filament. The filament undergoes a first order phase transition from the open chain to spiral conformation and shows a reentrant behavior in both the active extension and the turnover, defined as the ratio of attachment-detachment rates. Associated with the phase transition, the size and shape of the polymer change non-monotonically, and the relevant autocorrelation functions display a double-exponential decay. The corresponding correlation times show a maximum signifying the dominance of spirals. The orientational dynamics captures the rotation of spirals, and its correlation time decays with activity as a power law.

Active Brownian particles: mapping to equilibrium polymers and exact computation of moments.

It is well known that the path probabilities of Brownian motion correspond to the equilibrium configurational probabilities of flexible Gaussian polymers, while those of active Brownian motion correspond to in-extensible semiflexible polymers. Here we investigate the properties of the equilibrium polymer that corresponds to the trajectories of particles acted on simultaneously by both Brownian and active noise. Through this mapping we can see interesting crossovers in the mechanical properties of the polymer with changing contour length. The polymer end-to-end distribution exhibits Gaussian behaviour for short lengths, which changes to the form of semiflexible filaments at intermediate lengths, to finally go back to a Gaussian form for long contour lengths. By performing a Laplace transform of the governing Fokker-Planck equation of the active Brownian particle, we discuss a direct method to derive exact expressions for all the moments of the relevant dynamical variables, in arbitrary dimensions. These are verified via numerical simulations and used to describe interesting qualitative features such as, for example, dynamical crossovers. Finally we discuss the kurtosis of the ABP's position, which we compute exactly, and show that it can be used to differentiate between active Brownian particles and the active Ornstein-Uhlenbeck process.

A structure-dynamics relationship in ratcheted colloids: resonance melting, dislocations, and defect clusters.

We consider a two dimensional colloidal dispersion of soft-core particles driven by a one dimensional stochastic flashing ratchet that induces a time averaged directed particle current through the system. It undergoes a non-equilibrium melting transition as the directed current approaches a maximum associated with a resonance of the ratcheting frequency with the relaxation frequency of the system. We use extensive molecular dynamics simulations to present a detailed phase diagram in the ratcheting rate-mean density plane. With the help of a numerically calculated structure factor, solid and hexatic order parameters, and pair correlation functions, we show that the non-equilibrium melting is a continuous transition from a quasi-long range ordered solid to a hexatic phase. The transition is mediated by the unbinding of dislocations and formation of compact and string-like defect clusters.

Re-entrant phase separation in nematically aligning active polar particles.

We present a numerical study of the phase behavior of repulsively interacting active polar particles that align their active velocities nematically. The amplitude of the active velocity, and the noise in its orientational alignment control the active nature of the system. At high values of orientational noise, the structural fluid undergoes a continuous nematic-isotropic transition in active orientation. This transition is well separated from an active phase separation, characterized by the formation of high density hexatic clusters, observed at lower noise strengths. With increasing activity, the system undergoes a re-entrant fluid - phase separation - fluid transition. The phase coexistence at low activity can be understood in terms of motility induced phase separation. In contrast, the re-melting of hexatic clusters, and the collective motion at low orientational noise are dominated by flocking behavior. At high activity, sliding and jamming of polar sub-clusters, formation of grain boundaries, lane formation, and subsequent fragmentation of the polar patches mediate remelting.

Cell Boundary Confinement Sets the Size and Position of the E. coli Chromosome.

Although the spatiotemporal structure of the genome is crucial to its biological function, many basic questions remain unanswered on the morphology and segregation of chromosomes. Here, we experimentally show in Escherichia coli that spatial confinement plays a dominant role in determining both the chromosome size and position. In non-dividing cells with lengths increased to 10 times normal, single chromosomes are observed to expand > 4-fold in size. Chromosomes show pronounced internal dynamics but exhibit a robust positioning where single nucleoids reside robustly at mid-cell, whereas two nucleoids self-organize at 1/4 and 3/4 positions. The cell-size-dependent expansion of the nucleoid is only modestly influenced by deletions of nucleoid-associated proteins, whereas osmotic manipulation experiments reveal a prominent role of molecular crowding. Molecular dynamics simulations with model chromosomes and crowders recapitulate the observed phenomena and highlight the role of entropic effects caused by confinement and molecular crowding in the spatial organization of the chromosome.

Cross-linker mediated compaction and local morphologies in a model chromosome.

Chromatin and associated proteins constitute the highly folded structure of chromosomes. We consider a self-avoiding polymer model of the chromatin, segments of which may get cross-linked via protein binders that repel each other. The binders cluster together via the polymer mediated attraction, in turn, folding the polymer. Using molecular dynamics simulations, and a mean field description, we explicitly demonstrate the continuous nature of the folding transition, characterized by unimodal distributions of the polymer size across the transition. At the transition point the chromatin size and cross-linker clusters display large fluctuations, and a maximum in their negative cross-correlation, apart from a critical slowing down. Along the transition, we distinguish the local chain morphologies in terms of topological loops, inter-loop gaps, and zippering. The topologies are dominated by simply connected loops at the criticality, and by zippering in the folded phase.

Morphological and dynamical properties of semiflexible filaments driven by molecular motors.

We consider an explicit model of a semiflexible filament moving in two dimensions on a gliding assay of motor proteins, which attach to and detach from filament segments stochastically, with a detachment rate that depends on the local load experienced. Attached motor proteins move along the filament to one of its ends with a velocity that varies nonlinearly with the motor protein extension. The resultant force on the filament drives it out of equilibrium. The distance from equilibrium is reflected in the end-to-end distribution, modified bending stiffness, and a transition to spiral morphology of the polymer. The local stress dependence of activity results in correlated fluctuations in the speed and direction of the center of mass leading to a series of ballistic-diffusive crossovers in its dynamics.

Confinement and crowding control the morphology and dynamics of a model bacterial chromosome.

Motivated by recent experiments probing the shape, size and dynamics of bacterial chromosomes in growing cells, we consider a polymer model consisting of a circular backbone to which side-loops are attached, confined to a cylindrical cell. Such a model chromosome spontaneously adopts a helical shape, which is further compacted by molecular crowders to occupy a nucleoid-like sub-volume of the cell. With increasing cell length, the longitudinal size of the chromosome increases in a non-linear fashion until finally saturating, its morphology gradually opening up while displaying a changing number of helical turns. For shorter cells, the chromosome extension varies non-monotonically with cell size, which we show is associated with a radial to longitudinal spatial reordering of the crowders. Confinement and crowders constrain chain dynamics leading to anomalous diffusion. While the scaling exponent for the mean squared displacement of center of mass grows and saturates with cell length, that of individual loci displays a broad distribution with a sharp maximum.

Molecular Dynamics Simulation of a Feather-Boa Model of a Bacterial Chromosome.

The chromosome of a bacterium consists of a mega-base pair long circular DNA, which self-organizes within the micron-sized bacterial cell volume, compacting itself by three orders of magnitude. Unlike in eukaryotes, it lacks a nuclear membrane, and freely floats in the cytosol confined by the cell membrane. It is believed that strong confinement, cross-linking by associated proteins, and molecular crowding all contribute to determine chromosome size and morphology. Modeling the chromosome simply as a circular polymer decorated with closed side-loops in a cylindrical confining volume, has been shown to already recapture some of the salient properties observed experimentally. Here, we describe how a computer simulation can be set up to study structure and dynamics of bacterial chromosomes using this model.

Bidirectional motion of filaments: the role of motor proteins and passive cross linkers.

In eukaryotic cells, motor proteins (MPs) bind to cytoskeletal filaments and move along them in a directed manner generating active stresses. During cell division a spindle structure of overlapping antiparallel microtubules forms whose stability and dynamics under the influence of MPs have been studied extensively. Although passive cross linkers (PCLs) are known to provide structural stability to a filamentous network, consequences of the interplay between ATP dependent active forces of MPs and passive entropic forces of PCLs on filamentous overlap remain largely unexplored. Here, we formulate and characterize a model to study this, using linear stability analysis and numerical integration. In the presence of PCLs, we find dynamic phase transitions with changing activity exhibiting regimes of stable partial overlap with or without oscillations, instability towards complete overlap, and stable limit cycle oscillations that emerge via a supercritical Hopf bifurcation characterized by an oscillation frequency determined by the MP and PCL parameters. We show that the overlap dynamics and stability depend crucially on whether both the filaments of an overlapping pair are movable or one is immobilized, having potential implications for in vivo and in vitro studies.

Entropy production by active particles: Coupling of odd and even functions of velocity.

Nonequilibrium stochastic dynamics of several active Brownian systems are modeled in terms of nonlinear velocity dependent force. In general, this force may consist of both even and odd functions of velocity. We derive the expression for total entropy production in such systems using the Fokker-Planck equation. The result is consistent with the expression for stochastic entropy production in the reservoir that we obtain from probabilities of time-forward and time-reversed trajectories, leading to fluctuation theorems. Numerical simulation is used to find probability distribution of entropy production, which shows good agreement with the detailed fluctuation theorem.