Sergey V. Larin

Cooperation of TLR12 and TLR11 in the IRF8-dependent IL-12 response to Toxoplasma gondii profilin.

TLRs play a central role in the innate recognition of pathogens and the activation of dendritic cells (DCs). In this study, we establish that, in addition to TLR11, TLR12 recognizes the profilin protein of the protozoan parasite Toxoplasma gondii and regulates IL-12 production by DCs in response to the parasite. Similar to TLR11, TLR12 is an endolysosomal innate immune receptor that colocalizes and interacts with UNC93B1. Biochemical experiments revealed that TLR11 and TLR12 directly bind to T. gondii profilin and are capable of forming a heterodimer complex. We also establish that the transcription factor IFN regulatory factor 8, not NF-κB, plays a central role in the regulation of the TLR11- and TLR12-dependent IL-12 response of DCs. These results suggest a central role for IFN regulatory factor 8–expressing CD8+ DCs in governing the TLR11- and TLR12-mediated host defense against T. gondii.

Molecular-dynamics simulation of polyimide matrix pre-crystallization near the surface of a single-walled carbon nanotube

Polyimide-based composite materials with a single-walled carbon nanotube as filler were studied by means of extensive fully-atomistic molecular-dynamics simulations. Polyimides (PI) were considered based on 1,3-bis-(3′,4-dicarboxyphenoxy)-benzene (dianhydride R) and various types of diamines: 4,4′-bis-(4′′-aminophenoxy)-diphenylsulfone (diamine BAPS) and 4,4′-bis-(4′′-aminophenoxy)-diphenyl (diamine BAPB). The influence of the chemical structure of the polyimides on the microstructure of the composite matrix near the filler surface and away from it was investigated. The formation of subsurface layers close to the nanotube surface was found for all composites considered. In the case of R–BAPB-based composites, the formation of an organized structure was shown that could be the initial stage of the matrix crystallization process observed experimentally. Similar structural features were not observed in the R–BAPS composites. Carbon nanotubes induce the elongation of R–BAPB chains in composites whereas R–BAPS chains become more compact similar to what is observed for EXTEM™ polyimide. It was shown that electrostatic interactions do not influence the microstructure of composites but slow down significantly the dynamics of PI chains in composites.

Effect of the SO2 group in the diamine fragment of polyimides on their structural, thermophysical, and mechanical properties

Experimental and theoretical investigations, including an all-atom computer simulation, are performed for block samples of thermoplastic polyimides, amorphous R-BAPS (based on R dianhydride 1,3-bis(3′,4-dicarboxyphenoxy)benzene and diamine BAPS 4,4′-bis(4″-aminophenoxy)biphenyl sulfone), and crystallizable R-BAPB (based on R dianhydride and diamine BAPB 4,4’-bis(4″-aminophenoxy)biphenyl), which differ in either the presence or absence of the sulfone group in the repeating unit of the polyimide macromolecule. The features of thermophysical, structural, and mechanical properties of R-BAPS and R-BAPB are related to the formation of associates from sulfur and oxygen atoms of the sulfone group that are stabilized by electrostatic interactions.

Interpolyelectrolyte Complexes between Starlike and Linear Macromolecules: A Structural Model for Nonviral Gene Vectors

Molecular dynamics simulations are used to probe the structural organization of nonstoichiometric interpolyelectrolyte complexes (IPECs) formed by oppositely charged starlike and linear polyelectrolytes (PEs) in dilute aqueous solution. We demonstrate that undercompensated star-IPEC consists of a denser coacervate core and a charged starlike corona. Two distinctive populations of star branches completely embedded in a coacervate core and stretched in a lyophilizing corona are found. The scaling arguments support the stability of IPEC with partitioned star branches.

Linker Formation in an Overcharged Complex of Two Dendrimers and Linear Polyelectrolyte

The complexes formed by two dendrimers with charged terminal groups and oppositely charged long linear polyelectrolyte (LPE) have been studied using Brownian dynamics simulations. The structural properties of the complexes and their dependence on the LPE chain length were investigated. It was observed that dendrimers in the considered complexes are sufficiently overcharged; i.e., the number of adsorbed LPE monomers is larger than required for the neutralization. The degree of overcharging increases with the increase of the LPE length and is accompanied by the linker appearance until saturation in overcharging is reached. Nonmonotonic dependence of the linker size on the LPE length was observed. To describe the structural properties of the complexes formed by two macroions and a polyelectrolyte chain, the correlation theory has been developed.

Influence of the carbon nanofiller surface curvature on the initiation of crystallization in thermoplastic polymers

Experimental results have shown that graphitizated carbon nanofibers initiate crystallization in R-BAPB polyimides twice as fast as single-wall carbon nanotubes (CNT) leading to the hypothesis that nanofiller curvature influences polyimide crystallization. Therefore, atomistic molecular-dynamics simulations have been performed for R-BAPB in the presence of a flat graphene sheet and the results were compared with those obtained in the presence of a small-radius CNT. The polyimide chain segments tend to lie parallel to the nanofiller surface and this tendency is stronger and the segments are closer to the graphene surface than to the CNT one. Moreover, the density of the polyimide in the near-surface layer is higher for composites filled with graphene than with CNT. This confirms the assumption that the nanofiller surface curvature is indeed a factor influencing the polymer patterning structure, and that a smaller curvature (i.e. flat surface) provides an enhanced initiation of polymer ordering.

Evaluation of the characteristic equilibration times of bulk polyimides via full-atomic computer simulation

The full-atomic computer simulation of bulk plastic polyimides based on dianhydride 1,3-bis(3′,4-dicarboxyphenoxy)benzene and two types of diamines, 4,4′-bis(4″-aminophenoxy)diphenyl sulfone and 4,4′-bis(aminophenoxy)diphenyl oxide, is performed on the microsecond scale via the moleculardynamics method. For the investigated molecules, which consist of eight repeating units, the limiting values of the characteristic sizes of individual polymer chains are established. The limiting sizes obtained via computer simulation are in good agreement with theoretical values calculated in terms of virtual-bond formalism. It is found that the time of sample equilibration for the full-atomic computer simulation of bulk plastic polyimides is ∼1 μs, which agrees in order of magnitude with the displacement time of the center of mass of an individual molecule by a distance equal to its own size.

Influence of the carbon nanotube surface modification on the microstructure of thermoplastic binders

The structural properties of polymer nanocomposites based on thermoplastic polyimides filled with surface-modified carbon nanotubes (CNT) have been studied by means of fully-atomistic molecular-dynamics simulations. The influence of the distribution of functional carboxyl groups over the CNT surface on the polymer-matrix density distribution, and the orientational ordering of polymer chains have been investigated. It was shown that the polymer shifts far away from the nanoparticle surface with increase of the CNT modification degree. The orientational ordering of PI chains was not observed in the case of nanocomposites filled with modified CNTs where carboxyl groups are distributed uniformly on the surface. However, in case of the edge-modified CNTs the polymer can interact with the CNT surface; such edge-modified nanoparticles induce orientational ordering of crystallisable polyimide chains which can be considered as an initial stage of the polymer matrix crystallization.

Water-soluble nonstoichiometric complexes between sodium poly(styrenesulfonate) and cetylpyridinium chloride in aqueous NaCl solutions. A static and dynamic light scattering study.

Complexes formed between a cationic surfactant cetylpyridinium chloride, CPC, and an anionic polyelectrolyte sodium poly(styrenesulfonate), NaPSS, in aqueous 0.1 M NaCl solutions were studied by static and dynamic light scattering and by ζ-potential measurements in a broad region of surfactant cation, CP(+), to polyanion, PSS(-), charge ratio, S/P. Two NaPSS samples were used, NaPSS-L with a lower molar mass, M(w) = 1.4 × 10(5) g/mol, and NaPSS-H with a considerably higher M(w) (= 2.6 × 10(6) g/mol), to elucidate the effect of the polyion chain length on the behavior of the aggregates. In the polyelectrolyte-rich regime (S/P < 1), CPPSS complexes are soluble up to rather high S/P values (around 0.72, irrespective of the polyion chain length), which is attributed to a specific interaction between the hydrophobic benzene groups on the polyion and the surfactant micelle, which leads to a less efficient charge screening. The addition of surfactant causes chain contraction. The obtained data suggest a pronounced effect of the NaPSS chain length on the structural properties of the CPPSS complexes. The CPPSS-L complexes are small and dense (the radius of gyration, R(g), is 7.3 nm at S/P = 0.7), and their shape is close to spherical. In contrast, the CPPSS-H complexes (R(g) around 73 nm at S/P = 0.7) have no well-defined structure and reveal a stronger tendency toward intermolecular association when the nominal charge of the complex is reduced, although they remain pretty monodisperse. A model of a temporary network-like association in which surfactant micelles serve as cross-links for polyion chains is proposed to explain the behavior in CPPSS-H solutions. The forces responsible for such labile intermolecular association are weak, in contrast to strong specific interaction involved in the formation of the primary complex. The redissolution of the complex by adding excess surfactant (S/P > 1: the surfactant-rich regime) depends strongly on the polyion chain length and is a slow process, taking several days (CPPSS-L) or even weeks (CPPSS-H). It is achieved only at very high S/P values (around 240 and 2400 in the CPPSS-L and CPPSS-H cases, respectively) by hydrophobic binding of surfactant to the CPPSS complex. The predominating species in these solutions are free surfactant micelles. Similarly, a large excess of NaCl (almost 390 and 690 mol per 1 mol of CPPSS-L and CPPSS-H, respectively) is needed to disintegrate the stoichiometric CPPSS (S/P = 1) complex into free polyion chains and free surfactant micelles.

Structural effects in overcharging in complexes of hyperbranched polymers with linear polyelectrolytes

New insight is provided by a combined theoretical and simulational approach regarding the effects of structural characteristics of the constituents, on the overcharging phenomena in complexes formed by hyperbranched polymers with linear polyelectrolytes.