José G. Hernández Cifre

A Multiscale Scheme for the Simulation of Conformational and Solution Properties of Different Dendrimer Molecules

We propose a multiscale protocol for the simulation of conformation and dynamics of dendrimer molecules in dilute solution. Conformational properties (radius of gyration, mass distribution, and scattering intensities) and overall hydrodynamic properties (translational diffusion and intrinsic viscosity) are predicted by means of a very simple coarse-grained bead-and-spring model, whose parameters are not adjusted against experimental properties, but rather they are obtained from previous, atomic-level simulations which are also quite simple, performed with small fragments and Langevin dynamics simulation. The scheme is described and applied systematically to four different dendrimer molecules with up to seven generations. The predictive capability of this scheme is tested by comparison with experimental data. It is found that the predicted geometric and hydrodynamic radii of the dendrimer molecules are in agreement (typical error is about 4%) with a large set experimental values of the four dendrimers with various numbers of generations. Agreement with some X-ray scattering experimental intensities also confirms the good prediction of the internal structure. This scheme is easily extendable to study more complex molecules (e.g., functionalized dendrimers) and to simulate internal dynamics.

Comparison of Brownian dynamics algorithms with hydrodynamic interaction

The hydrodynamic interaction is an essential effect to consider in Brownian dynamics simulations of polymer and nanoparticle dilute solutions. Several mathematical approaches can be used to build Brownian dynamics algorithms with hydrodynamic interaction, the most common of them being the exact but time demanding Cholesky decomposition and the Chebyshev polynomial expansion. Recently, Geyer and Winter [J. Chem. Phys. 130, 1149051 (2009)] have proposed a new approximation to treat the hydrodynamic interaction that seems quite efficient and is increasingly used. So far, a systematic comparison among those approaches has not been clearly made. In this paper, several features and the efficiency of typical implementations of those approaches are evaluated by using bead-and-spring chain models. The different sensitivity to the bead overlap detected for the different implementations may be of interest to select the suitable algorithm for a given simulation.

Characterization of polyelectrolyte features in polysaccharide systems and mucin.

This review elucidates several aspects on the behavior of charged polysaccharides and mucin. Viscosification of dilute aqueous solutions of hyaluronan (HA) occurs in the course of time at low shear flow, whereas shear thinning as time evolves is found at moderate shear rates. Hydrogen bonds and electrostatic interaction play an important role for the emergence of these features. No time effect of the viscosity is observed for semidilute HA solutions. A degradation of HA is observed at low and high pH and this effect continues over long times, and it is only in the approximate interval 5<pH<10 that HA is stable. Small angle neutron scattering (SANS) measurements on semidilute aqueous solutions of mucin at pH=7 reveal a fractal dimension of 1.4, and the effect of temperature is insignificant on the fractal structure. This suggests that the mucin chains on a semi-local dimensional scale are rod-like. From various experimental methods on solutions of mucin it was found that at pH values around 2 (uncharged polymer), the intensive hydrophobic interactions lead to large association complexes, whereas at pH>>2 the negative charges suppress the tendency of forming associations. At pH<2, the mucin chains are compressed and they are decorated by some positive charges. In the semidilute regime, a fragmented network is developed. The intense association in semidilute solutions of mucin at pH=2 is further supported by the results from rheo-small angle light scattering measurements. Effects of ionic strength on the radius of gyration (R(g)) for dilute solutions of HA (pH=7) and positively charged hydroxyethylcellulose (HEC(+)) are studied with the aid of Monte Carlo simulations, and essential features of the polyelectrolyte effect on R(g) are captured in the computer simulation. Strong interactions are observed in aqueous mixtures of an anionic polysaccharide (HEC(-)) and an oppositely charged surfactant (cetyltrimethylammonium bromide; CTAB); this gives rise to extensive associations and macroscopic phase separation is approached. The massive association complexes are disclosed in the SANS experiments by a pronounced upturn in the scattered intensity at low values of the wave vector.

Effect of polyethylene glycol (PEG) length on the association properties of temperature-sensitive amphiphilic triblock copolymers (PNIPAAMm-b-PEGn-b-PNIPAAMm) in aqueous solution

Effects of temperature on the association behavior in aqueous solutions of a series of thermosensitive poly(N-isopropylacrylamide)-block-poly(ethylene glycol)-block-poly(N-isopropylacrylamide) triblock copolymers (PNIPAAMm-b-PEGn-b-PNIPAAMm) with the length of the PNIPAAM block fixed (m ≈ 67) and with different lengths of the PEG block (n = 23, 34, 77, and 165) have been studied with the aid of turbidity, dynamic light scattering (DLS), and Monte Carlo simulations. The turbidity results show that the sharp transition to high turbidity values is shifted to higher temperatures when the length of the PEG spacer is increased from 23 to 77, whereas no transition is observed for the longest PEG block. These findings are consistent with the DLS results, which suggest the formation of large association structures at temperatures well above the cloud point. The simulation results indicate that a long PEG-block portion separating the PNIPAAM blocks in the triblock copolymer reduces the tendency of the polymer forming interchain associations at elevated temperatures. Simulation shows that for a long PEG spacer, the copolymer moiety is rather extended even at high temperatures, whereas for copolymers with a short PEG length the thermoresponsive block copolymer undergoes a transition from an extended to a compact conformation.

Single-Molecule Behavior of Asymmetric Thermoresponsive Amphiphilic Copolymers in Dilute Solution

A bead-and-spring model has been used to simulate the behavior of thermoresponsive asymmetric diblock amphiphilic copolymers with aid of Monte Carlo simulations. The alteration of the thermodynamic conditions was mimicked by using a Lennard-Jones potential, which was related to the measured temperatures by comparison with experimental data for aqueous solutions of two sets of diblock copolymers, namely methoxypoly(ethylene glycol)-block-poly(N-isopropylacrylamide), one with different lengths of the hydrophilic block (MPEG(n)-b-PNIPAAM(71)) and one with varying lengths of the hydrophobic block (MPEG(57)-b-PNIPAAM(m)). The influence of the length of both the thermoresponsive and the hydrophilic block on the size and conformation of single molecules at various temperatures was studied by means of simulations. The temperature-induced contraction of the copolymer (MPEG(n)-b-PNIPAAM(71)) entities is only modestly affected by changing the length of the hydrophilic block, whereas for the MPEG(57)-b-PNIPAAM(m) copolymer both the transition temperature and the magnitude of the compression of the molecules are strongly influenced by the length of the thermosensitive block. When the MPEG chain fully covers the hydrophobic core, the copolymer moieties are stabilized, whereas poorly covered cores can promote interchain aggregation at elevated temperatures.

Aggregation behaviour of gold nanoparticles in presence of chitosan

Chitosan (CS) is a biocompatible polysaccharide with positive charge that is widely used as a coating agent for negatively charged nanoparticles. However, the types of structures that emerge by combining CS and nanoparticles as well as their behaviour are still poorly understood. In this work, we characterize the nanocomposites formed by gold nanoparticles (AuNPs) and CS and study the influence of CS in the expected aggregation process that should experience those nanoparticles under the favourable conditions of low pH and high ionic strength. Thus, at the working CS concentration, we observe the existence of CS structures that quickly trap the AuNPs and avoid the formation of nanoparticle aggregates in environmental conditions that, otherwise, would lead to such an aggregation.

Methods and Tools for the Prediction of Hydrodynamic Coefficients and Other Solution Properties of Flexible Macromolecules in Solution. A Tutorial Minireview

The calculation of solution properties of flexible macromolecules and other nanoparticles requires, in addition to the hydrodynamic formalisms needed for the sedimentation coefficient and other transport properties, the consideration of the conformational statistics and internal dynamics. The latter aspects can be handled with simulation methods like Monte Carlo and Brownian dynamics. An example of a Monte Carlo simulation for a model specific of DNA is illustrated with results for the several solution properties over an extremely wide range of molecular weight. The convenience of having computational tools of a quite general applicability has prompted us to implement the simulation and hydrodynamic treatments in software packages, MONTEHYDRO for Monte Carlo, and SIMUFLEX for Brownian dynamics which-with a scope similar to the HYDRO suite for rigid particles-can handle a variety of situations. As an application of the new methodology to a yet unclear problem in analytical ultracentrifugation, in a simple application of the SIMUFLEX software, we present a simulation of the so-called anomalous sedimentation of very long DNA molecules, obtaining results for the experimentally observable rotor-speed-dependence of the sedimentation coefficient.

Prediction of solution properties and dynamics of RNAs by means of Brownian dynamics simulation of coarse-grained models: Ribosomal 5S RNA and phenylalanine transfer RNA

BackgroundThe possibility of validating biological macromolecules with locally disordered domains like RNA against solution properties is helpful to understand their function. In this work, we present a computational scheme for predicting global properties and mimicking the internal dynamics of RNA molecules in solution. A simple coarse-grained model with one bead per nucleotide and two types of intra-molecular interactions (elastic interactions and excluded volume interactions) is used to represent the RNA chain. The elastic interactions are modeled by a set of Hooke springs that form a minimalist elastic network. The Brownian dynamics technique is employed to simulate the time evolution of the RNA conformations.ResultsThat scheme is applied to the 5S ribosomal RNA of E. Coli and the yeast phenylalanine transfer RNA. From the Brownian trajectory, several solution properties (radius of gyration, translational diffusion coefficient, and a rotational relaxation time) are calculated. For the case of yeast phenylalanine transfer RNA, the time evolution and the probability distribution of the inter-arm angle is also computed.ConclusionsThe general good agreement between our results and some experimental data indicates that the model is able to capture the tertiary structure of RNA in solution. Our simulation results also compare quite well with other numerical data. An advantage of the scheme described here is the possibility of visualizing the real time macromolecular dynamics.

Prediction of Solution Properties of Flexible-Chain Polymers: A Computer Simulation Undergraduate Experiment.

This paper describes a computational exercise at undergraduate level that demonstrates the employment of Monte Carlo simulation to study the conformational statistics of flexible polymer chains, and to predict solution properties. Three simple chain models, including excluded volume interactions, have been implemented in a public-domain computer program that is the tool on which this exercise is based. The first stage considers fundamental aspects of polymer chain statistics, such as the distribution of end-to-end distance and the exponents in the power laws that relate properties to chain length, for both ideal, phantom chains and also with excluded volume effects. The numerical results are employed to predict properties of real polymer/solvent systems, such as polystyrene in cyclohexane and toluene, which are then compared to experimental data.

Ionic strength effect in polyelectrolyte dilute solutions within the Debye-Huckel approximation: Monte Carlo and Brownian dynamics simulations

Two chain models, a Gaussian chain and a touching-beads (wormlike) chain, are used to represent a flexible polyelectrolyte (sodium polystyrene sulfonate) and a semiflexible polyelectrolyte (sodium alginate), respectively. Monte Carlo and Brownian dynamics simulations of those models were carried out to obtain the ionic strength dependence of some conformational and hydrodynamic properties expressed in form of equivalent radii. Electrostatic interactions were taken into account by the Debye–Hückel potential, thus counterions are not considered explicitly. In the case of the sodium polystyrene sulfonate model, a linear dependence of the equivalent radii with the ionic strength is found for a region of intermediate to low enough ionic strength values, whereas for high values of the ionic strength the equivalent radii reach a plateau with a value equal to that of the uncharged chain. Thus, an extrapolation to infinite ionic strength of the linear region would not report the actual property value of the uncharged chain. In the case of the sodium alginate model such a linear dependence is not so clearly appreciated. Our simulation results show a good agreement with several experimental data which support the validity of the Debye–Hückel approximation to model different types of polyelectrolyte solutions in a simple way.