Alexander V. Chertovich

Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

Recent advances enabled by the Hi-C technique have unraveled many principles of chromosomal folding that were subsequently linked to disease and gene regulation. In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. Mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principles of TAD folding in Drosophila melanogaster, we performed Hi-C and poly(A)(+) RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e., the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predicts TAD boundaries much worse than active chromatin marks do. Interestingly, inter-TADs correspond to decompacted inter-bands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin. We propose the mechanism of TAD self-assembly based on the ability of nucleosomes from inactive chromatin to aggregate, and lack of this ability in acetylated nucleosomal arrays. Finally, we test this hypothesis by polymer simulations and find that TAD partitioning may be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin.

Phase diagrams of block copolymer melts by dissipative particle dynamics simulations

Phase diagrams for monodisperse and polydisperse diblock copolymer melts and a random multiblock copolymer melt are constructed using dissipative particle dynamics simulations. A thorough visual analysis and calculation of the static structure factor in several hundreds of points at each of the diagrams prove the ability of mesoscopic molecular dynamics to predict the phase behavior of polymer systems as effectively as the self-consistent field-theory and Monte Carlo simulations do. It is demonstrated that the order-disorder transition (ODT) curve for monodisperse diblocks can be precisely located by a spike in the dependence of the mean square pressure fluctuation on χN, where χ is the Flory-Huggins parameter and N is the chain length. For two other copolymer types, the continuous ODTs are observed. Large polydispersity of both blocks obeying the Flory distribution in length does not shift the ODT curve but considerably narrows the domains of the cylindrical and lamellar phases partially replacing them with the wormlike micelle and perforated lamellar phases, respectively. Instead of the pure 3d-bicontinuous phase in monodisperse diblocks, which could be identified as the gyroid, a coexistence of the 3d phase and cylindrical micelles is detected in polydisperse diblocks. The lamellar domain spacing D in monodisperse diblocks follows the strong-segregation theory prediction, D∕N(1∕2) ~ (χN)(1∕6), whereas in polydisperse diblocks it is almost independent of χN at χN < 100. Completely random multiblock copolymers cannot form ordered microstructures other than lamellas at any composition.

Magnetic and viscoelastic response of elastomers with hard magnetic filler

Magnetic elastomers (MEs) based on a silicone matrix and magnetically hard NdFeB particles have been synthesized and their magnetic and viscoelastic properties have been studied depending on the size and concentration of magnetic particles and the magnetizing field. It has been shown that magnetic particles can rotate in soft polymer matrix under applied magnetic field, this fact leading to some features in both magnetic and viscoelastic properties. In the maximum magnetic field used magnetization of MEs with smaller particles is larger while the coercivity is smaller due to higher mobility of the particles within the polymer matrix. Viscoelastic behavior is characterized by long relaxation times due to restructuring of the magnetic filler under the influence of an applied mechanical force and magnetic interactions. The storage and loss moduli of magnetically hard elastomers grow significantly with magnetizing field. The magnetic response of the magnetized samples depends on the mutual orientation of the external magnetic field and the internal sample magnetization. Due to the particle rotation within the polymer matrix, the loss factor increases abruptly when the magnetic field is turned on in the opposite direction to the sample magnetization, further decreasing with time. Moduli versus field dependences have minimum at non-zero field and are characterized by a high asymmetry with respect to the field direction.

Anomalous Diffusion in Fractal Globules

The fractal globule state is a popular model for describing chromatin packing in eukaryotic nuclei. Here we provide a scaling theory and dissipative particle dynamics computer simulation for the thermal motion of monomers in the fractal globule state. Simulations starting from different entanglement-free initial states show good convergence which provides evidence supporting the existence of a unique metastable fractal globule state. We show monomer motion in this state to be subdiffusive described by ⟨X(2)(t)⟩∼t(αF) with αF close to 0.4. This result is in good agreement with existing experimental data on the chromatin dynamics, which makes an additional argument in support of the fractal globule model of chromatin packing.

Effect of nanotube size on the mechanical properties of elastomeric composites

Using a mesoscale coarse-grained model and dissipative particle dynamics, the mechanical properties of a cross-linked elastomer filled with surface-functionalized carbon nanotubes are investigated under uniaxial stretching, depending on nanotube length, nanotube bulk density, and crosslink density. Importantly, the system is deformed at equilibrium, allowing the cross-linked chains to be fully relaxed. Our results suggest that for a composite with chemical couplings between polymer and fillers, there actually exist different regimes of elastomer reinforcement, manifesting themselves in the stress–strain response, which is found to be dramatically dependent on the nanotube length L and the characteristic network mesh size : while the effect of the filler particles is relatively small at L −1 ∼ 1, there is a sharp increase in the mechanical modulus when L −1 ≫ 1.

Crumpled globule formation during collapse of a long flexible and semiflexible polymer in poor solvent

By introducing explicit solvent particles and hydrodynamic interactions we demonstrate that crumpled globules are formed after the collapse of long polymer chains (N = 10(4)) in a poor solvent. During the collapse crumples of all sizes form sequentially, but small crumples are not stable and convert to blobs with Gaussian statistics. The observed effective mean squared distance R(2)(n) ∼ n(0.38) at n > Ne and contact probability index p(n) ∼ n(-0.5) at n ≫ Ne, which is not following either the model of a fractal globule, or the predictions for an equilibrium globule. Polymer chain stiffness pushes the system to form globular crystallite, and this freezes crumpled structure with R(2)(n) ∼ n(0.33) at n > Ne as a stable state. We note that there is some similarity to crumple globule formation and crystallization of polymer melt.

Simulation of phase separation in melts of regular and random multiblock copolymers

The dissipative particle dynamics method and parallel computing are employed for computer simulation of phase separation in melts of regular and random (Markovian) AB multiblock copolymers of symmetric compositions. For the first time, it is shown that, as the Flory-Huggins parameter χ is increased, lamellar microstructures are formed in all these systems. At preset block length M, the microstructures arise in regular copolymers at lower χ values than those in random copolymers, while the formed lamellas are narrower and have smaller amounts of defects. At χM > 100, a superstrong segregation regime develops in the regular copolymers. In random copolymer melts, bicontinuous structures are observed for a long time; in the long run, they are likewise transformed into lamellar structures whose imperfection substantially increases with M.

Simulation of phase separation in melts of reacting multiblock copolymers

The dissipative particle dynamics method is employed to conduct the computer simulation of the phase separation occurring in a melt of a polymer containing monomer units of two types under the conditions of reversible polycondensation or interchain exchange. The chemical reactions are simulated via the Monte Carlo method. It is shown that growth in the Flory-Huggins parameter leads to macrophase separation, irrespective of the rate and type of the reactions and the spatial structure of an initial system. Relative changes in the probabilities of elementary reactions between units of different types shift the phase-transition point. Different levels of refinement are considered for description of the stationary states being developed. By the example of interchain exchange, it is shown that the structure of the polymer melt in the initial state can substantially affect the dynamics of the phase separation.

Conformation‐Dependent Sequence Design of HP Copolymers: An Algorithm Based on Sequential Modifications of Monomer Units

We present a new modification of the so-called conformation-dependent sequence design scheme for HP copolymers which was proposed several years ago (H and P refer to the hydrophobic and polar monomer units, respectively). New method models the real chemical experiments more realistically. We performed Monte Carlo computer simulations using the bond-fluctuation model for protein-like copolymers obtained by means of the new “iterative” method and compared the results with those obtained for originally proposed “instantaneous coloring” procedure. Copolymers designed by the “iterative” method are shown to have better-optimized functional properties. The investigation of the influence of sequence preparation conditions has revealed that the statistical properties of designed HP sequences depend rather strongly on the density of the parent homopolymer globule but not on the composition of H and P units.

Low Frequency Rheology of Magnetically Controlled Elastomers with Isotropic Structure

The method of torsion oscillations is used to measure the dynamic modulus of elasticity of magnetically controlled elastomers that comprise silicone rubber and carbonyl iron in the low-frequency (up to 100 Hz) range. The samples are synthesized in the absence of a magnetic field; therefore, they have an isotropic structure. In the measurements, a constant magnetic field (up to 24 kA/m) is superimposed along the axis of forced torsion oscillations of the sample. A simple model of the rheological behavior of magnetically controlled elastomers is proposed; the problem of torsion oscillations of a cylindrical sample is solved. From the comparison with the experiment for the materials under study, we determine the coefficients of the theoretical model and the corrections to them, which are made because of variations in the rheology of magnetically controlled elastomers under the influence of a magnetic field. The derived relations make it possible to exclude artifacts and to adequately describe dependences of the storage and loss moduli on the frequency of mechanical loading and the strength of the applied magnetic field.