Igor M. Neelov

Wet spinning of fibers made of chitosan and chitin nanofibrils

Biocompatible and bioresorbable composite fibers consisting of chitosan filled with anisotropic chitin nanofibrils with the length of 600-800 nm and cross section of about 11-12 nm as revealed by SEM and XRD were prepared by coagulation. Both chitin and chitosan components of the composite fibers displayed preferred orientations. Orientation of chitosan molecules induced by chitin nanocrystallites was confirmed by molecular modeling. The incorporation of 0.1-0.3 wt.% of chitin nanofibrils into chitosan matrix led to an increase in strength and Young modulus of the composite fibers.

Molecular Properties of Lysine Dendrimers and their Interactions with Aβ-Peptides and Neuronal Cells

Prevention of amyloidosis by chemical compounds is a potential therapeutic strategy in Alzheimers, prion and other neurodegenerative diseases. Regularly branched dendrimers and less regular hyperbranched polymers have been suggested as promising inhibitors of amyloid aggregation. As demonstrated in our previous studies, some widely used dendrimers (PAMAM, PPI) could not only inhibit amyloid aggregation in solution but also dissolve mature fibrils. In this study we have performed computer simulation of polylysine dendrimers of 3rd and 5th generations (D3 and D5) and analysed the effect of these dendrimers and some hyperbranched polymers on a lysine base (HpbK) on aggregation of amyloid peptide in solution. The effects of dendrimers on cell viability and their protective action against Aβ-induced cytotoxicity and alteration of K+channels was also analysed using human neuroblastoma SH-SY5Y cells. In addition, using fluorescence microscopy, we analysed uptake of FITC-conjugated D3 by SH-SY5Y cells and its distribution in the brain after intraventricular injections to rats. Our results demonstrated that dendrimers D3 and D5 inhibited amyloid aggregation in solution while HpbK enhanced amyloid aggregation. Cell viability and patch-clamp studies have shown that D3 can protect cells against Aβ-induced cytotoxicity and K+channel modulation. In contrast, HpbK had no protective effect against Aβ. Fluorescence microscopy studies demonstrated that FITC-D3 accumulates in the vacuolar compartments of the cells and can be detected in various brain structures and populations of cells after injections to the brain. As such, polylysine dendrimers D3 and D5 can be proposed as compounds for developing antiamyloidogenic drugs.

Conformational mobility of carbosilane dendrimer: Molecular dynamics simulation

Molecular dynamic simulations were carried out for carbosilane dendrimers of the 5th generation immersed in CCl4 solvent at different temperatures. The calculations were accomplished by using the AMBER force field in the united atom approximation. Lennard-Jones particles were considered as the solvent molecules with potential parameters corresponding to CCl4. There was one molecule of a dendrimer in each calculation cell, and the cells size was large enough to exclude any interaction between dendrimers. The internal structure of the dendrimer (density distributions for both dendrimer and solvent atoms) as well as dynamics of trans–gauche transitions of single bonds and fluctuations of branching points were analysed. It was shown that the one barrier mechanism of conformational transitions observed earlier in linear polymers occurs to be valid also for the conformational rearrangements in dendrimers with the hindered rotation around chain bonds. The contribution of rotational restrictions is essential only for branching points, which are close to the core.

Mathematical simulation of lysine dendrimers: Temperature dependences

The mathematical simulation of second- and fourth-generation lysine dendrimers is performed via the molecular-dynamics method. Temperature dependences of primary structural characteristics are obtained. It is shown that the sizes and atomic distributions of these dendrimers are weakly temperature-dependent. Together with the structural properties, the local mobility of CH2 groups in the dendrimers is investigated via the molecular-dynamics method and NMR spectroscopy. It is shown that the orientational mobility of internal groups of the lysine dendrimers is lower than that of terminal groups, in agreement with the data available for flexible-chain dendrimers. Changes in correlation times with temperature are well described by the Arrhenius dependence. At the same time, the orientational mobility of internal groups in the lysine dendrimers depends on the generation number. This behavior is different from that of flexible-chain dendrimers, in which the mobility of internal groups is the same for dendrimers of different generations.

Mechanism of shear deformation of a coiled myosin coil: Computer simulation

Polymer coiled coils are composed of entangled linear chains in a helical conformation. Their mechanical characteristics are interesting because these structures are involved in the composition of natural fibrillar structures. The method of molecular dynamics is used for the simulation of stretching at a constant rate for a superhelical fragment of myosin protein composed of two identical α helices containing 126 amino acid residues in each helix. The case of shear deformation of a molecule is considered (the load is applied to the N terminus of one chain and to the C terminus of another chain). In this case of loading, slippage of chains with respect to each other can occur. Deformation of a molecule proceeds in several stages. At the initial stage, the superhelix is unfolded and there is a gradual unfolding of end fragments of individual α helices; this process is accompanied by their displacement with respect to the helical fragment of the neighboring chain. In this case, the reaction force increases. At the second stage of stretching, the process passes to the mechanism of deformation when, in the central part of the molecule, α-helical fragments of both chains unfold. In this region, the reaction-force-extension curve shows a plateau region. Between unfolded fragments, new hydrophobic contacts and hydrogen bonds are formed, and fragments of the β structure emerge. Once all turns of α helices in the central parts of the molecule are unfolded, the mechanism of deformation changes and further extension of a molecule proceeds via straightening of previously unfolded central fragments, a process that is accompanied by an increase in the reaction force. When chains achieve their limiting extension, slippage commences with an accompanying decrease in the reaction force.

Conformational variability of helix sense reversals in poly(methyl isocyanate)

The conformations and energies of several helix sense reversal geometries in poly(methyl isocyanate) (PMIC) have been determined using the PCFF forcefield. In an extension of previous studies, a larger conformational variability for a helix sense reversal has been investigated. In addition to the reversal geometry previously detailed by several authors that results in a relatively small angle deviation from the rod-like polyisocyanate structure, we report the discovery of reversals of similar energy with much larger angle deviations from linearity. The effect of electrostatic interactions as controlled by the value of the dielectric constant, e, on the conformation and energy of a reversal is also shown to be important. At e=1.0 (vacuum) the conformations of the reversals with large and small angle ‘kinks’ have similar energies. However, at e=2.0 (non-polar organic solvent) and e=3.5 (bulk state) the reversals corresponding to the large angle kinks have lower energies.

Self-Assembly of Lysine-Based Dendritic Surfactants Modeled by the Self-Consistent Field Approach

Implementing a united atom model, we apply self-consistent field theory to study structure and thermodynamic properties of spherical micelles composed of surfactants that combine an alkyl tail with a charged lysine-based dendritic headgroup. Following experiments, the focus was on dendron surfactants with varying tail length and dendron generations G0, G1, G2. The heads are subject to acetylation modification which reduces the charge and hydrophilicity. We establish a reasonable parameter set which results in semiquantitative agreement with the available experiments. The critical micellization concentration, aggregation number, and micelle size are discussed. The strongly charged dendronic surfactants micelles are stable for generation numbers G0 and G1, for progressively higher ionic strengths. Associates of G2 surfactants are very small and can only be found at extreme surfactant concentration and salt strengths. Micelles of corresponding weaker charged acetylated variants exist up to G2, tolerate significantly lower salt concentrations, but lose the spherical micelle topology for G0 at high ionic strengths.

Molecular dynamics simulations of polymers of unsubstituted and substituted poly(p-phenylene terephthalate)s in the bulk state

A molecular dynamics simulation has been canied out on polymers of p-phenylene terephthalate (PPT) and 1,4-phenylene-2-octyloxy terephthalate (PTA8) It six different temperatures: 300 K, 375 K. 450 K, 575 K. 500 K, and 625 K, The periodic simulation boxes consisted of 18 (PPT) or 16 (PTA8) chains with 9 monomer units. The Compass force field was used in the simulations. The crystallographic data and density obtained from mulation at room temperature agreed well with the experimental data of PPT. Our simulations showed that, in the case of PTA8, the crystal → layered nematics phase transition temperature (T m ) is close to the experimental value for the polymer similar to PTA8. The average initial structure was obtained from X-ray scattering data. The simulated X-ray dara indicated the existence of a biaxial nematic phase, in accordance with experimental findings.

Brownian dynamics of polymer chains in external fields of different symmetry

Abstract The dependence of the normal modes relaxation time, τ, on the scale of motion, Λ, for a freely jointed polymer chain in the presence of an orienting field of dipole symmetry was obtained both analytically and by the method of Brownian dynamics. Comparison with the results for the case of a quadrapole field obtained earlier shows that the field symmetry influences mainly the prefactor in the dependence τ(Λ) reflecting the mobility of single chain element in the field.

Structure and properties of polydisperse polyelectrolyte brushes studied by self-consistent field theory

Two complementary self-consistent field theoretical approaches are used to analyze the equilibrium structure of binary and ternary brushes of polyions with different degrees of polymerization. Stratification in binary brushes is predicted: the shorter chains are entirely embedded in the proximal sublayer depleted of end-points of longer chains while the peripheral sublayer contains exclusively terminal segments of longer chains. The boundary between sublayers is enriched with counterions that neutralize the residual charge of the proximal sublayer. These analytical predictions for binary brushes are confirmed and extended to ternary brushes using the numerical Scheutjens-Fleer approach.