Arthi Jayaraman

Understanding the Effect of Polylysine Architecture on DNA Binding Using Molecular Dynamics Simulations

Polycations with varying chemistries and architectures have been synthesized and used in DNA transfection. In this paper we connect poly-L-lysine (PLL) architecture to DNA-binding strength, and in turn transfection efficiency, since experiments have shown that graft-type oligolysine architectures [e.g., poly(cyclooctene-g-oligolysine)] exhibit higher transfection efficiency than linear PLL. We use atomistic molecular dynamics simulations to study structural and thermodynamic effects of polycation-DNA binding for linear PLL and grafted oligolysines of varying graft lengths. Structurally, linear PLL binds in a concerted manner, while each oligolysine graft binds independently of its neighbors in the grafted architecture. Additionally, the presence of a hydrophobic backbone in the grafted architecture weakens binding to DNA compared to linear PLL. The binding free energy varies nonmonotonically with the graft length primarily due to entropic contributions. The binding free energy normalized to the number of bound amines is similar between the grafted and linear architectures at the largest (Poly5) and smallest (Poly2) graft length and stronger than the intermediate graft lengths (Poly3 and Poly4). These trends agree with experimental results that show higher transfection efficiency for Poly3 and Poly4 grafted oligolysines than for Poly5, Poly2, and linear PLL.

Structure and assembly of dense solutions and melts of single tethered nanoparticles

The microscopic polymer reference interaction site model theory is generalized and applied to study intermolecular pair correlation functions and collective structure factors of dense solutions and melts of spherical nanoparticles carrying a single tethered chain. The complex interplay of entropy (translational, conformational, and packing) and enthalpy (particle-particle attraction) leads to different structural arrangements with distinctive small and wide angle scattering signatures. Strong concentration fluctuations, indicative of aggregate formation and/or a tendency for microphase separation, occur as the total packing fraction and/or particle-particle attraction strength increase. In analogy with block copolymers, the microphase spinodal curve is estimated by extrapolation of the inverse of the amplitude of the small angle scattering peak. For nanoparticles that are twice the diameter of monomers, the microphase separation boundary spinodal occurs at higher particle-particle attraction strength (or lower temperature) as compared to the macrophase demixing curve for nanoparticles with no tethers when the packing fraction is below 0.45, while the opposite trend is observed above 0.45. Increasing nanoparticle diameter results in a reduction in the microphase spinodal temperature and a qualitative change in its packing fraction dependence.

Effect of the Number and Placement of Polymer Tethers on the Structure of Concentrated Solutions and Melts of Hybrid Nanoparticles

We have generalized and applied the microscopic polymer reference interaction site model theory to study intermolecular pair correlation functions and collective structure factors of concentrated solutions and melts of spherical nanoparticles carrying one, two, or four tethered polymer chains. A complex interplay of entropy (translational, conformational, and packing) and enthalpy (particle-particle attraction) leads to different structural arrangements with distinctive small- and wide-angle scattering signatures. Strong concentration fluctuations indicative of aggregate formation and/or a tendency for microphase separation occur as the total packing fraction and/or particle-particle attraction strength increase. In analogy with block copolymers, the microphase spinodal curve is estimated by extrapolation of the inverse of the amplitude of the small-angle scattering peak. As the number of tethered chains on nanoparticles increases, the microphase separation boundary spinodal occurs at higher particle-particle attraction strength or lower temperature. For nanoparticles with two tethers, increasing the angle between the attached chains shifts the microphase spinodal to lower temperatures. For nanoparticles with four tethers, the structural correlations are insensitive to various symmetric placements. The tendency for microphase transition is enhanced upon asymmetrically placing all four tethers on one side of the particle due to the high anisotropy of steric hindrance.

Effect of bidispersity in grafted chain length on grafted chain conformations and potential of mean force between polymer grafted nanoparticles in a homopolymer matrix

In efforts to produce polymeric materials with tailored physical properties, significant interest has grown around the ability to control the spatial organization of nanoparticles in polymer nanocomposites. One way to achieve controlled particle arrangement is by grafting the nanoparticle surface with polymers that are compatible with the matrix, thus manipulating the interfacial interactions between the nanoparticles and the polymer matrix. Previous work has shown that the molecular weight of the grafted polymer, both at high grafting density and low grafting density, plays a key role in dictating the effective inter-particle interactions in a polymer matrix. At high grafting density nanoparticles disperse (aggregate) if the graft molecular weight is higher (lower) than the matrix molecular weight. At low grafting density the longer grafts can better shield the nanoparticle surface from direct particle-particle contacts than the shorter grafts and lead to the dispersion of the grafted particles in the matrix. Despite the importance of graft molecular weight, and evidence of non-trivial effects of polydispersity of chains grafted on flat surfaces, most theoretical work on polymer grafted nanoparticles has only focused on monodisperse grafted chains. In this paper, we focus on how bidispersity in grafted chain lengths affects the grafted chain conformations and inter-particle interactions in an implicit solvent and in a dense homopolymer polymer matrix. We first present the effects of bidispersity on grafted chain conformations in a single polymer grafted particle using purely Monte Carlo (MC) simulations. This is followed by calculations of the potential of mean force (PMF) between two grafted particles in a polymer matrix using a self-consistent Polymer Reference Interaction Site Model theory-Monte Carlo simulation approach. Monte Carlo simulations of a single polymer grafted particle in an implicit solvent show that in the bidisperse polymer grafted particles with an equal number of short and long grafts at low to medium grafting density, the short grafts are in a more coiled up conformation (lower radius of gyration) than their monodisperse counterparts to provide a larger free volume to the longer grafts so they can gain conformational entropy. The longer grafts do not show much difference in conformation from their monodisperse counterparts at low grafting density, but at medium grafting density the longer grafts exhibit less stretched conformations (lower radius of gyration) as compared to their monodisperse counterparts. In the presence of an explicit homopolymer matrix, the longer grafts are more compressed by the matrix homopolymer chains than the short grafts. We observe that the potential of mean force between bidisperse grafted particles has features of the PMF of monodisperse grafted particles with short grafts and monodisperse grafted particles with long grafts. The value of the PMF at contact is governed by the short grafts and values at large inter-particle distances are governed by the longer grafts. Further comparison of the PMF for bidisperse and monodisperse polymer grafted particles in a homopolymer matrix at varying parameters shows that the effects of matrix chain length, matrix packing fraction, grafting density, and particle curvature on the PMF between bidisperse polymer grafted particles are similar to those seen between monodisperse polymer grafted particles.

Wetting-Dewetting and Dispersion-Aggregation Transitions Are Distinct for Polymer Grafted Nanoparticles in Chemically Dissimilar Polymer Matrix.

Simulations and experiments are conducted on mixtures containing polymer grafted nanoparticles in a chemically distinct polymer matrix, where the graft and matrix polymers exhibit attractive enthalpic interactions at low temperatures that become progressively repulsive as temperature is increased. Both coarse-grained molecular dynamics simulations, and X-ray scattering and neutron scattering experiments with deuterated polystyrene (dPS) grafted silica and poly(vinyl methyl ether) PVME matrix show that the sharp phase transition from (mixed) dispersed to (demixed) aggregated morphologies due to the increasingly repulsive effective interactions between the blend components is distinct from the continuous wetting-dewetting transition. Strikingly, this is unlike the extensively studied chemically identical graft-matrix composites, where the two transitions have been considered to be synonymous, and is also unlike the free (ungrafted) blends of the same graft and matrix homopolymers, where the wetting-dewetting is a sharp transition coinciding with the macrophase separation.

Interaction of hyaluronan binding peptides with glycosaminoglycans in poly(ethylene glycol) hydrogels.

This study investigates the incorporation of hyaluronan (HA) binding peptides into poly(ethylene glycol) (PEG) hydrogels as a mechanism to bind and retain hyaluronan for applications in tissue engineering. The specificity of the peptide sequence (native RYPISRPRKRC vs non-native RPSRPRIRYKC), the role of basic amino acids, and specificity to hyaluronan over other GAGs in contributing to the peptide–hyaluronan interaction were probed through experiments and simulations. Hydrogels containing the native or non-native peptide retained hyaluronan in a dose-dependent manner. Ionic interactions were the dominating mechanism. In diH2O the peptides interacted strongly with HA and chondroitin sulfate, but in phosphate buffered saline the peptides interacted more strongly with HA. For cartilage tissue engineering, chondrocyte-laden PEG hydrogels containing increasing amounts of HA binding peptide and exogenous HA had increased retention and decreased loss of cell-secreted proteoglycans in and from the hydrogel at 28 days. This new matrix-interactive hydrogel platform holds promise for tissue regeneration.

Integrating PRISM theory and Monte Carlo simulation to study polymer-functionalised particles and polymer nanocomposites

Polymer nanocomposites consist of nanoscale additives embedded in a polymer matrix and are widely used in the automobiles, optics and microelectronics industries. Since the composition and the morphology of the polymer nanocomposite impact its macroscopic properties, significant efforts have been made to understand how parameters, such as polymer and nanoparticle chemistries, molecular weight of the matrix polymers and nanoparticle size, help tune the morphology. Theory and simulations have proven to be useful tools in this field due to their ability to link molecular level interactions, the morphology and the macroscopic properties. Due to the computational intensity of molecular simulations of a dense polymer matrix, there has been a strong effort on the theoretical front to develop methodologies that map out equilibrium structure and phase behaviour of polymer nanocomposites over a large parameter space. In this paper, we review the details of the self-consistent polymer reference interaction site model (PRISM)–Monte Carlo (MC) simulation method which integrates theory and simulation to study phase behaviour in polymer nanocomposites. We discuss two specific cases of polymer nanocomposites containing polymer-grafted nanoparticles with chemical and physical heterogeneity in grafts in which this self-consistent PRISM–MC approach has been used to study effective inter-filler interactions and phase behaviour.

Polydisperse homopolymer grafts stabilize dispersions of nanoparticles in a chemically identical homopolymer matrix: an integrated theory and simulation study

This paper presents a computational study of the effect of polydispersity in grafted polymers on the effective interactions between polymer grafted nanoparticles in a polymer matrix, when graft and matrix polymers are chemically identical. The potential of mean force (PMF) between grafted particles, calculated using a self-consistent PRISM theory-Monte Carlo simulation approach, shows that graft polydispersity weakens the attractive well at intermediate inter-particle distances, eliminating the well completely at high polydispersity index (PDI). The elimination of the mid-range attractive well is due to the longer grafts in the polydisperse distribution that introduce steric repulsion at large distances, and the increased wetting of the grafted layer by matrix chains arising from reduced monomer crowding within the polydisperse grafted layer. Trends in how the PMF changes as a function of grafting density, ratio of matrix to graft length, and packing fraction of polymer matrix seen for monodisperse grafts are preserved for polydisperse grafts. Comparison of a log-normal distribution to a bidisperse distribution of chain lengths (with equal number of short and long chains) with the same PDI and average length, shows that the polydisperse distribution can better stabilize dispersions than the bidisperse distributions because of the longer chains in the polydisperse distribution. Additionally, in a bidisperse distribution, with all chains shorter than the matrix chain length, there is a reduction in the mid-range attraction, thus confirming the role of reduced monomer crowding in the bidisperse grafted layer in increasing the grafted layer wetting by the matrix chains, and, as a result, improving miscibility of grafted particles and matrix.

Assembly of copolymer functionalized nanoparticles: a Monte Carlo simulation study

Functionalizing nanoparticles with copolymer ligands is an attractive method to tailor the assembly of the nanoparticles. We use Monte Carlo simulation to demonstrate how the monomer sequence in the grafted copolymers is a tuning parameter to control assembly of nanoparticles, and the shapes, sizes and structures of the assembled nanoclusters. We have studied spherical nanoparticles grafted with AB copolymers with alternating or diblock sequences, and a range of monomer chemistries by varying strengths of like-monomer (A–A and/or B–B) attractive interactions in the presence of either relatively strong or negligible unlike-monomer (A–B) repulsive interaction. In the presence of negligible A–B repulsions the alternating sequence produces nanoclusters that are relatively isotropic regardless of whether A–A or B–B monomers are attractive, while the diblock sequence produces nanoclusters that are smaller and more compact when the block closer to the surface (A–A) is attractive and larger loosely held together clusters when the outer block (B–B) is attractive. In the presence of strong A–B repulsions the alternating sequence leads to either particle dispersion or smaller clusters than those at negligible A–B repulsions; for the diblock sequence strong and negligible A–B repulsions exhibit similar cluster characteristics. Additionally, diblock copolymer grafted particles tend to assemble into anisotropic shapes despite the isotropic grafting of the copolymer chains on the particle surface. Particle size and graft length balance enthalpic gain and entropic losses coming from inter-grafted particle contacts and/or inter- and intra-grafted chain contacts within the same grafted particle, and in turn dictates the shape and size of the cluster. For constant graft length and when A–A attractions are stronger than B–B attractions, diblock copolymer grafted particles form long “caterpillar-like” structures with large particle diameters, and short nanowires with small particle diameters. In the dilute concentration regime a small increase in the particle concentration does not change the cluster characteristics confirming that the structure within a cluster is primarily governed by the copolymer functionalization imparting a “valency” to the nanoparticle “atom”. This work illustrates how copolymer functionalization and tuning the grafted copolymer sequence could be an exciting new route experimentalists can take to tailor self-assembly of nanoparticles into target nanostructures.

Liquid state theory of the structure and phase behaviour of polymer-tethered nanoparticles in dense suspensions, melts and nanocomposites

We have studied the structure and phase behaviour of spherical nanoparticles grafted with a modest number of polymer tethers in the dense suspension and pure melt states, and dissolved in a homopolymer matrix, using the polymer reference interaction site model integral equation theory. In the absence of a polymer matrix, fluids of tethered nanoparticles exhibit strong concentration fluctuations indicative of aggregate formation and/or a tendency for microphase separation as the total packing fraction and/or nanoparticle attraction strength increase. For nanoparticles of core diameter twice that of the monomer, carrying one, two and four tethers, the microphase spinodal temperature grows roughly as a power-law function of packing fraction. As the number of polymer tethers increases, the microphase spinodal curve shifts to lower temperatures due to steric shielding of the nanoparticle core. In the presence of a homopolymer matrix, the microphase spinodal curve of single-tethered particles exhibits both dilution-like and depletion-like features and a non-monotonic dependence of the spinodal temperature on matrix chain length. As the number of tethers is increased, the microphase curves become more dilution-like and the effect of matrix degree of polymerisation, particle size and tether length on the apparent spinodal temperature diminishes.