Structure and dynamics of double-stranded DNA rotaxanes.

A DNA rotaxane, with its unique mechanically interlocked architecture consisting of a circular DNA molecule threaded onto a linear DNA axle, holds promise as a fundamental component for nanoscale functional devices. Nevertheless, its structural and dynamic behaviors, essential for advancing molecular machinery, remain largely unexplored. Using extensive all-atom molecular dynamics simulations, we investigated the behaviors of double-stranded DNA (dsDNA) rotaxanes, concentrating on the effects of shape distortion induced by torsional stress in small circular dsDNA containing 70-90 base pairs. We analyzed structural characteristics, including shape, intermolecular distances, and tilt angles, while also exploring dynamic properties such as translational diffusion and toroidal rotation. Our results indicate that shape distortion brings the circular and linear dsDNA components into closer proximity and causes a slight increase in translational diffusion yet a minor decrease in toroidal rotation. Nevertheless, there is no apparent evidence of coupling between translation and rotation. Overall, the insights from this study indicate that such shape distortion does not significantly alter their structure and dynamics. This finding provides flexibility for the design of DNA rotaxanes in nanoscale applications.

Design of a Brownian ratchet based on repetitive aggregation and dispersion of stimuli-responsive molecules.

We propose a Brownian ratchet for the unidirectional transport of stimuli-responsive molecules confined in a series of asymmetric geometries. It relies on repetitive cycles of aggregation and dispersion, which cause significant changes in molecular distribution within the confining geometry and enable the Brownian motion of the molecules to be ratcheted in a specific direction. To demonstrate the feasibility of the proposed Brownian ratchet, we conducted Brownian dynamics simulations where stimuli-responsive molecules were repeatedly aggregated and dispersed in a series of truncated conical tubes by altering intermolecular interactions. These simulations demonstrated the unidirectional transport of the molecules, indicating the efficacy of the proposed Brownian ratchet. Furthermore, we found that it becomes more effective with higher concentrations of molecules. This study suggests that, through the deliberate control of molecular assembly and disassembly by stimuli-responsive intermolecular interactions, it is possible to achieve directional and controlled molecular transport in various nanoscale applications.

Brownian ratchet for directional nanoparticle transport by repetitive stretch-relaxation of DNA.

Brownian motion subject to a periodic and asymmetric potential can be biased by external, nonequilibrium fluctuations, leading to directional movement of Brownian particles. Sequence-dependent flexibility variation along double-stranded DNA has been proposed as a tool to develop periodic and asymmetric potentials for DNA binding of cationic nanoparticles with sizes below tens of nanometers. Here, we propose that repetitive stretching and relaxation of a long, double-stranded DNA molecule with periodic flexibility gradient can induce nonequilibrium fluctuations that tune the amplitude of asymmetric potentials for DNA-nanoparticle binding to result in directional transport of nanometer-sized particles along DNA. Realization of the proposed Brownian ratchet was proven by Brownian dynamics simulations of coarse-grained models of a single, long DNA molecule with flexibility variation and a cationic nanoparticle.

Liquid-like properties of cyclopentadienyl complexes of barium: molecular dynamics simulations of nanoscale droplets.

Cyclopentadienyl complexes of barium have great utility in materials science and engineering, in particular, as precursors in the atomic layer deposition processes, which are required to be fluidic as well as thermally stable and volatile. Here, we investigated the liquid-like properties of cyclopentadienyl barium complexes including (Me5C5)2Ba, (tBu3C5H2)2Ba, (iPr4C5H)2Ba, (iPr5C5)2Ba, and [(SiMe3)3C5H2]2Ba, using molecular dynamics simulations of nanoscale droplets. The compounds were modeled using a recently developed generic force field, GFN-FF. Nanoscale droplets with about 5.0 nm diameters were formed by aggregating 96 molecules of each compound. Simulation results reveal that substituting methyl groups of (Me5C5)2Ba with other alkyl and silyl moieties has a non-negligible effect on the intra- and intermolecular structure and dynamics. In particular, in contrast to more flexible (Me5C5)2Ba, the substitution with five iso-propyl groups to form (iPr5C5)2Ba adds rigidity to the complex with restricted orientational fluctuations for two cyclopentadienyl ligands and arranges molecules parallel to each other with greater probability. In addition, comparison between (tBu3C5H2)2Ba, with three tert-butyl groups, and its silyl analogue, [(SiMe3)3C5H2]2Ba, reveals that intermolecular interactions between the molecules with silyl groups are softer than those with tert-butyl groups and result in broader radial distribution functions, whereas the dynamic properties are similar for both compounds. This work suggests that molecular dynamics simulations contribute to molecular-level understanding of the effect of chemical substitution in organometallic compounds on the intra- and intermolecular properties of molecular liquids.

A model for cascading failures with the probability of failure described as a logistic function.

In most cascading failure models in networks, overloaded nodes are assumed to fail and are removed from the network. However, this is not always the case due to network mitigation measures. Considering the effects of these mitigating measures, we propose a new cascading failure model that describes the probability that an overloaded node fails as a logistic function. By performing numerical simulations of cascading failures on Barabási and Albert (BA) scale-free networks and a real airport network, we compare the results of our model and the established model describing the probability of failure as a linear function. The simulation results show that the difference in the robustness of the two models depends on the initial load distribution and the redistribution of load. We further investigate the conditions of our new model under which the network exhibits the strongest robustness in terms of the load distribution and the network topology. We find the optimal value for the parameter of the load distribution and demonstrate that the robustness of the network improves as the average degree increases. The results regarding the optimal load distribution are verified by theoretical analysis. This work can be used to develop effective mitigation measures and design networks that are robust to cascading failure phenomena.

Potential of Mean Force for DNA Wrapping Around a Cationic Nanoparticle.

Sharp bending and wrapping of DNA around proteins and nanoparticles (NPs) has been of extensive research interest. Here, we present the potential of mean force (PMF) for wrapping a DNA double helix around a cationic NP using coarse-grained models of a double-stranded DNA and a cationic NP. Starting from a NP wrapped around by DNA, the PMF was calculated along the distance between the center of the NP and one end of the DNA molecule. A relationship between the distance and the extent of DNA wrapping is used to calculate the PMF as a function of DNA wrapping around a NP. In particular, the PMF was compared for two DNA sequences of (AT)25/(AT)25 and (AC)25/(GT)25, for which the persistence lengths are different by ∼10 nm. The simulation results provide solid evidence of the thermodynamic preference for complex formation of a cationic NP with more flexible DNA over the less flexible DNA. Furthermore, we estimated the elastic energy of DNA bending, which was in good order-of-magnitude agreement with the theoretical prediction of elastic rods. This work suggests that the variation of sequence-dependent DNA flexibility can be utilized in DNA nanotechnologies, in which the position and dynamics of NPs are regulated on large-scale DNA structures, or the structural transformation of DNA is triggered by the sequence-dependent binding of NPs.

Sequence-dependent twist-bend coupling in DNA minicircles.

Looping of double-stranded DNA molecules with 100-200 base pairs into minicircles, catenanes, and rotaxanes has been suggested as a potential tool for DNA nanotechnologies. However, sharp DNA bending into a minicircle with a diameter of several to ten nanometers occurs with alterations in the DNA helical structure and may lead to defective kink formation that hampers the use of DNA minicircles, catenanes, and rotaxanes in nanoscale DNA applications. Here, we investigated local variations of a helical twist in sharply bent DNA using microsecond-long all-atom molecular dynamics simulations of six different DNA minicircles, focusing on the sequence dependence of the coupling between DNA bending and its helical twist. Twist angles between consecutive base pairs were analyzed at different locations relative to the direction of DNA bending and, among 10 unique dinucleotide steps, we identified four dinucleotide steps with strong twist-bend coupling, the pyrimidine-purine dinucleotide steps of TA/TA, CG/CG, and CA/TG and the purine-purine dinucleotide step of GA/TC. This work suggests the sequence-dependent structural responses of DNA to strong mechanical deformation, providing new molecular-level insights into the structure and stability of sharply bent DNA minicircles for nanoscale applications.

Effect of DNA Flexibility on Complex Formation of a Cationic Nanoparticle with Double-Stranded DNA.

We present extensive molecular dynamics simulations of a cationic nanoparticle and a double-stranded DNA molecule to discuss the effect of DNA flexibility on the complex formation of a cationic nanoparticle with double-stranded DNA. Martini coarse-grained models were employed to describe double-stranded DNA molecules with two different flexibilities and cationic nanoparticles with three different electric charges. As the electric charge of a cationic nanoparticle increases, the degree of DNA bending increases, eventually leading to the wrapping of DNA around the nanoparticle at high electric charges. However, a small increase in the persistence length of DNA by 10 nm requires a cationic nanoparticle with a markedly increased electric charge to bend and wrap DNA around. Thus, a more flexible DNA molecule bends and wraps around a cationic nanoparticle with an intermediate electric charge, whereas a less flexible DNA molecule binds to a nanoparticle with the same electric charge without notable bending. This work provides solid evidence that a small difference in DNA flexibility (as small as 10 nm in persistence length) has a substantial influence on the complex formation of DNA with proteins from a biological perspective and suggests that the variation of sequence-dependent DNA flexibility can be utilized in DNA nanotechnology as a new tool to manipulate the structure of DNA molecules mediated by nanoparticle binding.

Tracer Diffusion in Tightly-Meshed Homogeneous Polymer Networks: A Brownian Dynamics Simulation Study.

We report Brownian dynamics simulations of tracer diffusion in regularly crosslinked polymer networks in order to elucidate the transport of a tracer particle in polymer networks. The average mesh size of homogeneous polymer networks is varied by assuming different degrees of crosslinking or swelling, and the size of a tracer particle is comparable to the average mesh size. Simulation results show subdiffusion of a tracer particle at intermediate time scales and normal diffusion at long times. In particular, the duration of subdiffusion is significantly prolonged as the average mesh size decreases with increasing degree of crosslinking, for which long-time diffusion occurs via the hopping processes of a tracer particle after undergoing rattling motions within a cage of the network mesh for an extended period of time. On the other hand, the cage dynamics and hopping process are less pronounced as the mesh size decreases with increasing polymer volume fractions. The interpretation is provided in terms of fluctuations in network mesh size: at higher polymer volume fractions, the network fluctuations are large enough to allow for collective, structural changes of network meshes, so that a tracer particle can escape from the cage, whereas, at lower volume fractions, the fluctuations are so small that a tracer particle remains trapped within the cage for a significant period of time before making infrequent jumps out of the cage. This work suggests that fluctuation in mesh size, as well as average mesh size itself, plays an important role in determining the dynamics of molecules and nanoparticles that are embedded in tightly meshed polymer networks.

Intervertebral Disc Regeneration Using Stem Cell/Growth Factor-Loaded Porous Particles with a Leaf-Stacked Structure.

Although biological therapies based on growth factors and transplanted cells have demonstrated some positive outcomes for intervertebral disc (IVD) regeneration, repeated injection of growth factors and cell leakage from the injection site remain considerable challenges for human therapeutic use. Herein, we prepare human bone marrow-derived mesenchymal stem cells (hBMSCs) and transforming growth factor-ß3 (TGF-ß3)-loaded porous particles with a unique leaf-stack structural morphology (LSS particles) as a combination bioactive delivery matrix for degenerated IVD. The LSS particles are fabricated with clinically acceptable biomaterials (polycaprolactone and tetraglycol) and procedures (simple heating and cooling). The LSS particles allow sustained release of TGF-ß3 for 18 days and stable cell adhesiveness without additional modifications of the particles. On the basis of in vitro and in vivo studies, it was observed that the hBMSCs/TGF-ß3-loaded LSS particles can provide a suitable milieu for chondrogenic differentiation of hBMSCs and effectively induce IVD regeneration in a beagle dog model. Thus, therapeutically loaded LSS particles offer the promise of an effective bioactive delivery system for regeneration of various tissues including IVD.

Home Range Estimates and Habitat Use of Siberian Flying Squirrels in South Korea.

Conservation measures or management guidelines must be based on species' ecological data. The home range of the target species was studied to understand its spatial ecology, in order to protect it. The Siberian flying squirrel is the only flying squirrel species present and is considered as a protected species in South Korea. In this study, we investigated the home range, habitat use, and daily movement of Siberian flying squirrels from February 2015 to June 2016 at Mt. Baekwoon, Gangwon Province, South Korea. We tracked 21 flying squirrels using radio transmitters and analyzed the home range of 12 individuals. Flying squirrels appeared to have an overall mean home range of 18.92 ± 14.80 ha with a core area of 3.54 ha ± 3.88 ha. Movement activity peaked between 18:00-19:00 with the longest distance traveled, coinciding with sunset. In addition, we observed the preference of Siberian flying squirrels to the old deciduous forest with dense crowns. The results of the present study indicate that it is important to manage their habitat; for instance, preserving an appropriate size of mature deciduous forest is essential for Siberian flying squirrels. While our study provides needed baseline information on the spatial activity of the species, further research on topics such as the national distribution, behavior, and population dynamics of Siberian flying squirrels is needed in South Korea.

Nematic ordering of hard rods under strong confinement in a dense array of nanoposts.

The effect of confinement on the behavior of liquid crystals is interesting from a fundamental and practical standpoint. In this work, we report Monte Carlo simulations of hard rods in an array of hard nanoposts, where the surface-to-surface separations between nanoposts are comparable to or less than the length of hard rods. This particular system shows promise as a means of generating large-scale organization of the nematic liquid by introducing an entropic external field set by the alignment of nanoposts. The simulations show that nematic ordering of hard rods is enhanced in the nanopost arrays compared with that in bulk, in the sense that the nematic order is significant even at low concentrations at which hard rods remain isotropic in bulk, and the enhancement becomes more significant as the passage width between two nearest nanoposts decreases. An analysis of local distribution of hard-rod orientations at low concentrations with weak nematic ordering reveals that hard rods are preferentially aligned along nanoposts in the narrowing regions between two curved surfaces of nearest nanoposts; hard rods are less ordered in the passages and in the centers of interpost spaces. It is concluded that at low concentrations the confinement in a dense array of nanoposts induces the localized nematic order first in the narrowing regions and, as the concentration further increases, the nematic order spreads over the whole region. The formation of a well-ordered phase at low concentrations of hard rods in a dense array of nanoposts can provide a new route to the low-concentration preparation of nematic liquid crystals that can be used as anisotropic dispersion media.

The breakdown of the local thermal equilibrium approximation for a polymer chain during packaging.

The conformational relaxation of a polymer chain often slows down in various biological and engineering processes. The polymer, then, may stay in nonequilibrium states throughout the process such that one may not invoke the local thermal equilibrium (LTE) approximation, which has been usually employed to describe the kinetics of various processes. In this work, motivated by recent single-molecule experiments on DNA packaging into a viral capsid, we investigate how the nonequilibrium conformations and the LTE approximation would affect the packaging of a polymer chain into small confinement. We employ a simple but generic coarse-grained model and Langevin dynamics simulations to investigate the packaging kinetics. The polymer segments (both inside and outside the confinement) stay away from equilibrium under strong external force. We devise a simulation scheme to invoke the LTE approximation during packaging and find that the relaxation of nonequilibrium conformations plays a critical role in regulating the packaging rate.

Transport dynamics of complex fluids.

Thermal motion in complex fluids is a complicated stochastic process but ubiquitously exhibits initial ballistic, intermediate subdiffusive, and long-time diffusive motion, unless interrupted. Despite its relevance to numerous dynamical processes of interest in modern science, a unified, quantitative understanding of thermal motion in complex fluids remains a challenging problem. Here, we present a transport equation and its solutions, which yield a unified quantitative explanation of the mean-square displacement (MSD), the non-Gaussian parameter (NGP), and the displacement distribution of complex fluids. In our approach, the environment-coupled diffusion kernel and its time correlation function (TCF) are the essential quantities that determine transport dynamics and characterize mobility fluctuation of complex fluids; their time profiles are directly extractable from a model-free analysis of the MSD and NGP or, with greater computational expense, from the two-point and four-point velocity autocorrelation functions. We construct a general, explicit model of the diffusion kernel, comprising one unbound-mode and multiple bound-mode components, which provides an excellent approximate description of transport dynamics of various complex fluidic systems such as supercooled water, colloidal beads diffusing on lipid tubes, and dense hard disk fluid. We also introduce the concepts of intrinsic disorder and extrinsic disorder that have distinct effects on transport dynamics and different dependencies on temperature and density. This work presents an unexplored direction for quantitative understanding of transport and transport-coupled processes in complex disordered media.

Directional Ostwald Ripening for Producing Aligned Arrays of Nanowires.

The remarkable electronic and mechanical properties of nanowires have great potential for fascinating applications; however, the difficulties of assembling ordered arrays of aligned nanowires over large areas prevent their integration into many practical devices. In this paper, we show that aligned VO2 nanowires form spontaneously after heating a thin V2O5 film on a grooved SiO2 surface. Nanowires grow after complete dewetting of the film, after which there is the formation of supercooled nanodroplets and subsequent Ostwald ripening and coalescence. We investigate the growth mechanism using molecular dynamics simulations of spherical Lennard-Jones particles, and the simulations help explain how the grooved surface produces aligned nanowires. Using this simple synthesis approach, we produce self-aligned, millimeter-long nanowire arrays with uniform metal-insulator transition properties; after their transfer to a polymer substrate, the nanowires act as a highly sensitive array of strain sensors with a very fast response time of several tens of milliseconds.

In silico construction of a flexibility-based DNA Brownian ratchet for directional nanoparticle delivery.

Brownian particles confined in a system with periodic and asymmetric potential can be transported in a specific direction along the potential by repetitively switching the potential on and off. Here, we propose a DNA-based Brownian ratchet for directional transport of positively charged nanoparticles in which nanoparticle delivery follows the path dictated by a single, long, double-stranded DNA. We performed Brownian dynamics simulations to prove its realization using coarse-grained models. A periodic and asymmetric potential for nanoparticle binding is constructed along a single, long, double-stranded DNA molecule by a novel strategy that uses variation in sequence-dependent DNA flexibility. Directional and processive motion of nanoparticles is achieved by changing salt concentration repetitively over several cycles to switch the asymmetric potential on and off. This work suggests that double-stranded DNA molecules with elaborately designed flexibility variation can be used as a molecule-scale guide for spatial and dynamic control of nanoparticles for future applications.

New Method for Constant- NPT Molecular Dynamics.

The well-established molecular dynamics simulation methods for constant- NPT ensemble systems such as the Andersen-Nosé-Hoover method and their variants may alter the dynamic properties of the molecules under consideration, because their equations of motion are modified by the coupling with thermostat or barostat. To circumvent this artifact, we propose a new molecular dynamics simulation algorithm, by which only the molecules near the wall of the simulation box are coupled to the thermostat and barostat and the molecules of interest placed in the inner part of the simulation box remain intact. We test the efficiency of our algorithm in attaining the target temperature and pressure and the conformity of the calculated equilibrium and dynamic properties to those of a constant- NPT ensemble system.

Vesicle-like assemblies of ligand-stabilized nanoparticles with controllable membrane composition and properties.

Here, we report that nanoparticles modified with simple end-functionalized alkyl thiol ligands show interesting directional self-assembly behavior and can act as an effective surfactant to encapsulate other functional molecules and nanoparticles. Gold nanoparticles modified with the mixture of alkyl thiols and hydroxyl-terminated alkyl thiols organize into unique vesicle-like structures with controllable membrane thicknesses. Molecular dynamics simulations showed that the ligand segregation and the edge-to-edge ligand binding are responsible for the two-dimensional assembly formation. Furthermore, the nanoparticle assemblies can encapsulate other functional nanoparticles into the membrane or inside the cavity, generating multicomponent inorganic vesicles with various morphologies. The light-induced release profiles of encapsulated dye molecules showed that the membrane properties can be controlled by varying the membrane thickness and ligand composition.

Entropic effect of macromolecular crowding enhances binding between nucleosome clutches in heterochromatin, but not in euchromatin.

Sharp increase in macromolecular crowding induces abnormal chromatin compaction in the cell nucleus, suggesting its non-negligible impact on chromatin structure and function. However, the details of the crowding-induced chromatin compaction remain poorly understood. In this work, we present a computer simulation study on the entropic effect of macromolecular crowding on the interaction between chromatin structural units called nucleosome clutches. Nucleosome clutches were modeled by a chain of nucleosomes collapsed by harmonic restraints implicitly mimicking the nucleosome association mediated by histone tails and linker histones. The nucleosome density of the clutches was set close to either that of high-density heterochromatin or that of low-density euchromatin. The effective interactions between these nucleosome clutches were calculated in various crowding conditions, and it was found that the increase in the degree of macromolecular crowding induced attractive interaction between two clutches with high nucleosome density. Interestingly, the increased degree of macromolecular crowding did not induce any attraction between two clutches with low nucleosome density. Our results suggest that the entropic effect of macromolecular crowding can enhance binding between nucleosome clutches in heterochromatin, but not in euchromatin, as a result of the difference in nucleosome packing degrees.

Directional rolling of positively charged nanoparticles along a flexibility gradient on long DNA molecules.

Directing the motion of molecules/colloids in any specific direction is of great interest in many applications of chemistry, physics, and biological sciences, where regulated positioning or transportation of materials is highly desired. Using Brownian dynamics simulations of coarse-grained models of a long, double-stranded DNA molecule and positively charged nanoparticles, we observed that the motion of a single nanoparticle bound to and wrapped by the DNA molecule can be directed along a gradient of DNA local flexibility. The flexibility gradient is constructed along a 0.8 kilobase-pair DNA molecule such that local persistence length decreases gradually from 50 nm to 40 nm, mimicking a gradual change in sequence-dependent flexibility. Nanoparticles roll over a long DNA molecule from less flexible regions towards more flexible ones as a result of the decreasing energetic cost of DNA bending and wrapping. In addition, the rolling becomes slightly accelerated as the positive charge of nanoparticles decreases due to a lower free energy barrier of DNA detachment from charged nanoparticle for processive rolling. This study suggests that the variation in DNA local flexibility can be utilized in constructing and manipulating supramolecular assemblies of DNA molecules and nanoparticles in structural DNA nanotechnology.