Semi-stiff Polymers Research Articles

Therapeutic nanoworms: towards novel synthetic dendritic cells for immunotherapy

A new class of antibody-functionalized, semi-flexible and filamentous polymers (diameter 5–10 nm, length ∼200 nm) with a controlled persistence length, a high degree of stereoregularity and the potential for multiple simultaneous receptor interactions has been developed. We have decorated these highly controlled, semi-stiff polymers with T cell activating anti-CD3 antibodies and analyzed their application potential as simple synthetic mimics of dendritic cells (sDCs). Our sDCs do not only activate T cells at significantly lower concentrations than free antibodies or rigid sphere-like counterparts (PLGA particles) but also induce a more robust T cell response. Our novel design further yields sDCs that are biocompatible and non-toxic. The observed increased efficacy highlights the importance of architectural flexibility and multivalency for modulating T cell response and cellular function in general.

Role of non-uniform confinement in shape transitions of semi-stiff polymers

New types of nanostructures are constantly being developed synthetically but are also found in biological systems. Specific examples include the production of carbon nanocones as well as the conical core in some viruses. Such conical structures can be used to investigate the role of non-uniform confinement on the stability of e.g. toroidal structures formed by semi-stiff circular polymers, such as DNA. In this communication we are interested in the principal features of the compaction process. Using an external field and a conical confinement we observe several distinct shape transitions from a circle-like shape to several toroidal-like loops for both a two-dimensional and a three-dimensional system. The thermodynamic stability of these toroidal-like structures was investigated by evaluating their relative free energies using Monte Carlo simulations in the Extended Ensemble in the case of a two-dimensional system and by observing a hysteresis of the compaction-extension curve for the three-dimensional case.

A Review of Monte Carlo Simulations of Polymers with PERM

In this review, we describe applications of the pruned-enriched Rosenbluth method (PERM), a sequential Monte Carlo algorithm with resampling, to various problems in polymer physics. PERM produces samples according to any given prescribed weight distribution, by growing configurations step by step with controlled bias, and correcting "bad" configurations by "population control". The latter is implemented, in contrast to other population based algorithms like e.g. genetic algorithms, by depth-first recursion which avoids storing all members of the population at the same time in computer memory. The problems we discuss all concern single polymers (with one exception), but under various conditions: Homopolymers in good solvents and at the $\Theta$ point, semi-stiff polymers, polymers in confining geometries, stretched polymers undergoing a forced globule-linear transition, star polymers, bottle brushes, lattice animals as a model for randomly branched polymers, DNA melting, and finally -- as the only system at low temperatures, lattice heteropolymers as simple models for protein folding. PERM is for some of these problems the method of choice, but it can also fail. We discuss how to recognize when a result is reliable, and we discuss also some types of bias that can be crucial in guiding the growth into the right directions.

Method for sampling compact configurations for semistiff polymers

The sampling of compact configurations is crucial when investigating structural properties of semistiff polymers, like proteins and DNA, using Monte Carlo methods. A sampling scheme for a continuous model based on configuration biasing is introduced, tested, and compared with conventional methods. The proposed configuration biased Monte Carlo method, used together with the Wang-Landau sampling scheme, enables us to obtain any thermodynamic property within the statistical ensemble in use. Using the proposed method, it is possible to collect statistical data of interest for a wide range of compactions (from stretched up to several toroid loops) in a single computer experiment. A second-order-like stretched-toroid phase transition is observed for a semistiff polymer, and the critical temperature is estimated.

Semistiff polymer model of unfolded proteins and its application to NMR residual dipolar couplings

We present a new statistical model of unfolded proteins in which the stiffness of polypeptide backbone is taken into account. We construct and solve a mean field equation which has the form of a diffusion equation and derive the distribution function for conformations of unfolded polypeptides. Accounting for the stiffness of the protein backbone results in a more accurate description of general properties of a polypeptide chain, such as its gyration radius. We then use the distribution function of a semistiff protein within a previously developed theoretical framework [J. Biomol. NMR 39, 1 (2007)] to determine the nuclear magnetic resonance (NMR) residual dipolar couplings (RDCs) in unfolded proteins. The calculated RDC profiles (dependence of the RDC value on the residue number) exhibit a more prominent bell-like shape and a better agreement with experimental data as compared to the previous results obtained with the random flights chain model.

Deformations of promoter DNA bound to carcinogens help interpret effects on TATA-element structure and activity.

The TATA-box binding protein (TBP) is required by eukaryotic RNA polymerases for correct transcription initiation. TBP binds to the minor groove of an 8 base pair (bp) DNA-promoter element known as the TATA box and severely bends the TATA box. The promoter-DNA substrate can be damaged by components present in the cell or the environment to produce covalent carcinogen-DNA adducts. These may lead to transcription blockage or unfaithful transcription. Benzo[a]pyrene (BP) is a widespread environmental chemical carcinogen which can be metabolically converted to DNA-reactive enantiomeric (+) and (-)-anti-benzo[a]pyrene diol epoxides (BPDEs). Recent experimental studies of a pair of stereoisomeric adenine adducts, derived from (+) and (-)-anti-BPDEs, have revealed how these lesions influence the complexation of TBP with the TATA box. Depending on the adduct's location in the TATA box and its stereochemistry, the stability of monomeric TATA-TBP complexes was found to increase or decrease relative to the unmodified DNA. We report here analyses of molecular-dynamics simulations to interpret these findings. Structural analyses of 12 DNA-protein systems representing different combinations of adduct stereoisomer type and placement within the promoter reveal that the location of the adduct within the TATA octamer determines whether the stability of TATA-TBP complexes is increased or decreased. The effect on binding stability can be interpreted in terms of conformational freedom and major-groove space available to BP due to the hydrogen bonds and inserted phenylalanines of the TATA-TBP complex; that is, depending on the position of the adenine to which BP is covalently bound, BP can be accommodated in an intercalated or major-groove orientation with ease or with difficulty (due to interference with TATA-TBP interactions). The unravelled structures and interactions thus reveal the effect of different adduct locations on TATA-TBP complex formation and suggest how transcription initiation may be affected by the presence of a bulky BP.

Melt rheology of poly(lactic acid): Entanglement and chain architecture effects

Poly(lactic acids) (PLAs) are a family of polyesters available via fermentation from renewable resources and are the subject of considerable recent commercial attention. In this study, the melt rheological properties of a family of poly(lactic acid) stars are investigated and compared to the properties of the linear material. For polymers made from a 98:2 ratio of the L to D enantiomeric monomers it is found that the entanglement molecular weight is in the range of 9000 g per mole (Me≈8700 g/mol) while the molecular weight for branch entanglement is inferred to be approximately 3500 g per mole (Mb≈34 600 g/mol). In addition, the zero shear viscosity of the linear material increases with the 4.6 power of molecular weight. These results may suggest that PLA is a semistiff polymer in accordance with other recent findings. The increase in zero shear viscosity for the branched materials is measured and quantified in terms of appropriate enhancement factors. Relaxation spectra show that the transition zone for the linear and branched materials are nearly indistinguishable, while the star polymers have greater contributions to the terminal regime. The effects of chain architecture on the flow activation are found to be modest, implying that small scale motions in PLA homopolymers largely control this phenomenon. Good agreement is found between the dynamic data and many aspects of the theory of star polymers, however, a dependence of the zero shear viscosity on the number of arms is observed.

Phase Transitions of Single Semistiff Polymer Chains

We study numerically a lattice model of semiflexible homopolymers with nearest neighbor (nn) attraction and energetic preference for straight joints between bonded monomers. For this we use a new Monte Carlo algorithm, the “prunedenriched Rosenbluth Method” (PERM). It is very efficient both for relatively open configurations at high temperatures and for compact and frozen-in low-T states. This allows us to study in detail the phase diagram as a function of nn attractione and stiffnessx. It shows aθ-collapse line with a transition from open coils (smalle) to molten compact globules (largee) and a freezing transition toward a state with orientational global order (large stiffnessx). Qualitatively this is similar to a recently studied mean-field theory [S. Doniach, T. Garel, and H. Orland (1996),J. Chem. Phys. 105(4), 1601], but there are important differences in details. In contrast to the mean-field theory and to naive expectations, theθ-temperatureincreases with stiffnessx. The freezing temperature increases even faster, and reaches theθ-line at a finite value ofx. For even stiffer chains, the freezing transition takes place directly, without the formation of an intermediate globular state. Although being in conflict with mean-field theory, the latter had been conjectured already by Doniachet al. on the basis of heuristic arguments and of low-statistics Monte Carlo simulations. Finally, we discuss the relevance of the present model as a very crude model for protein folding.