Theory and Simulations of Macromolecular Soft Materials: Linking Molecular Design to Macroscale Morphology and Function

We use theory and simulation techniques to connect molecular features of macromolecular materials, specifically polymers, to their morphology and macroscopic properties, thereby guiding synthesis of materials for various applications in the energy and biomedical fields. In the first part of my talk I will present our recent theory and simulation studies of polymer functionalized nanoparticles in polymer nanocomposites. The goal of this work is to control spatial arrangement of nanoparticles in a polymer nanocomposite so as to engineer materials with target mechanical or optical properties. One can tailor the inter-particle interactions and precisely control the assembly of the particles in the polymer matrix by functionalizing nanoparticle surfaces with polymers, and systematically tuning the composition, chemistry, molecular weight and grafting density of these grafted polymers. We have developed an integrated self-consistent approach involving Polymer Reference Interaction Site Model (PRISM) theory and molecular simulations to study polymer grafted nanoparticles in polymer matrix, and understand the effect of heterogeneity, such as monomer chemistry, monomer sequence, and polydispersity, in the polymer functionalization on the effective interactions, and dispersion/assembly of functionalized nanoparticles in a polymer matrix. In the second part of my talk I will present our molecular simulation studies aimed at designing polycations for DNA delivery. DNA delivery involves successful transfection of therapeutic DNA by a vector into target cells and expression of that genetic material. Viral vectors, while effective, can elicit harmful immunogenic responses, thus motivating ongoing research on non-viral transfection agents. Cationic polymers or polycations are a promising class of non-viral vectors due to their low immugenic responses and low toxicity, and their ability to bind to the polyanionic DNA backbone to form a polycation-DNA complex (polyplex) that is then internalized in the target cell. Combinatorial approaches have generated many polycations with differing DNA transfection efficacies, but there is a need for general design guidelines that can relate the molecular features of the polycation to its DNA transfection efficiency. Using atomistic and coarse-grained molecular dynamics simulations of DNA and polycations composed of polypeptides, we connect the thermodynamics of polycation-DNA binding and structure of the polycation-DNA complexes, both of which impact transfection efficiency, to polycation chemistry and architecture

Experimental and theoretical evidence for molecular forces driving surface segregation in photonic colloidal assemblies

Surface segregation in binary colloidal mixtures offers a simple way to control both surface and bulk properties without affecting their bulk composition. Here, we combine experiments and coarse-grained molecular dynamics (CG-MD) simulations to delineate the effects of particle chemistry and size on surface segregation in photonic colloidal assemblies from binary mixtures of melanin and silica particles of size ratio (Dlarge/Dsmall) ranging from 1.0 to similar to 2.2. We find that melanin and/or smaller particles segregate at the surface of micrometer-sized colloidal assemblies (supraballs) prepared by an emulsion process. Conversely, no such surface segregation occurs in films prepared by evaporative assembly. CG-MD simulations explain the experimental observations by showing that particles with the larger contact angle (melanin) are enriched at the supraball surface regardless of the relative strength of particle-interface interactions, a result with implications for the broad understanding and design of colloidal particle assemblies

Effect of Oligopeptide Orientation on Polymer-based DNA Delivery

Non-viral synthetic gene therapy reagents offer excellent structural and chemical versatility within non-immunogenic delivery systems, coupled with high therapeutic gene carrying capacity and long shelf life, making them attractive alternatives to viral systems. The success of non-viral transfection using polymers hinges on efficient nuclear uptake of nucleic acid cargo and overcoming intra- and extracellular barriers. This poster will describe the integration of the PKKKRKV heptapeptide (the Simian virus SV40 large T-antigen nuclear localization sequence, NLS) onto a polymer backbone, and the resultant high reporter gene expression in mice when administered by intramuscular ultrasound-mediated delivery. These novel polymers afforded protein expression higher than JetPEI™ in vivo, and in cell culture outperformed commercial reagents JetPEI™ and Lipofectamine 2000™, the latter being notorious for coupling high transfection efficiency with cytotoxicity. The orientation of the NLS peptide grafts relative to the polymer backbone markedly affected transfection performance both in vitro and in vivo. Quantitative polymerase chain reaction (qPCR) studies on transfected cells showed that polymers having the NLS attached at the valine residue afforded higher nuclear translocation, and subsequently higher protein expression, relative to those having the NLS groups attached in the opposite orientation. Besides nuclear uptake, the superior binding characteristics of these comb polymers compared to linear polylysine, as judged by atomistic and coarse grain simulations as well as polymer-DNA binding experiments, contributes to their enhanced transfection performance. Polyplexes formed from these comb polymer structures exhibit low cytotoxicity and high transfection efficiency both in vitro and in vivo, demonstrating the therapeutic promise of these novel gene therapy reagents

Structural Color Production in Melanin-based Disordered Colloidal Nanoparticle Assemblies in Spherical Confinement

Melanin is a ubiquitous natural pigment that exhibits broadband absorption and high refractive index. Despite its widespread use in structural color production, how the absorbing material, melanin, affects the generated color is unknown. Using a combined molecular dynamics and finite-difference time-domain computational approach, this paper investigates structural color generation in one-component melanin nanoparticle-based supra-assemblies (called supraballs) as well as binary mixtures of melanin and silica (non-absorbing) nanoparticle-based supraballs. Experimentally produced one-component melanin and one-component silica supraballs, with thoroughly characterized primary particle characteristics using neutron scattering, produce reflectance profiles similar to the computational analogues, confirming that the computational approach correctly simulates both absorption and multiple scattering from the self-assembled nanoparticles. These combined approaches demonstrate that melanin's broadband absorption increases the primary reflectance peak wavelength, increases saturation, and decreases lightness factor. In addition, the dispersity of nanoparticle size more strongly influences the optical properties of supraballs than packing fraction, as evidenced by production of a larger range of colors when size dispersity is varied versus packing fraction. For binary melanin and silica supraballs, the chemistry-based stratification allows for more diverse color generation and finer saturation tuning than does the degree of mixing/demixing between the two chemistries.Comment: 40 pages, Figure

Modeling Structural Colors from Disordered One-Component Colloidal Nanoparticle-based Supraballs using Combined Experimental and Simulation Techniques

Bright, saturated structural colors in birds have inspired synthesis of self-assembled, disordered arrays of assembled nanoparticles with varied particle spacings and refractive indices. However, predicting colors of assembled nanoparticles, and thereby guiding their synthesis, remains challenging due to the effects of multiple scattering and strong absorption. Here, we use a computational approach to first reconstruct the nanoparticles' assembled structures from small-angle scattering measurements and then input the reconstructed structures to a finite-difference time-domain method to predict their color and reflectance. This computational approach is successfully validated by comparing its predictions against experimentally measured reflectance and provides a pathway for reverse engineering colloidal assemblies with desired optical and photothermal properties.Comment: 14 pages, 3 figures, 1 ToC figur

Mechanism of Structural Colors in Binary Mixtures of Nanoparticle-based Supraballs

Inspired by structural colors in avian species, various synthetic strategies have been developed to produce non-iridescent, saturated colors using nanoparticle assemblies. Mixtures of nanoparticles varying in particle chemistry (or complex refractive indices) and particle size have additional emergent properties that impact the color produced. For such complex multi-component systems, an understanding of assembled structure along with a robust optical modeling tool can empower scientists to perform intensive structure-color relationship studies and fabricate designer materials with tailored color. Here, we demonstrate how we can reconstruct the assembled structure from small-angle scattering measurements using the computational reverse-engineering analysis for scattering experiments (CREASE) method and then use the reconstructed structure in finite-difference time-domain (FDTD) calculations to predict color. We successfully, quantitatively predict experimentally observed color in mixtures containing strongly absorbing melanin nanoparticles and demonstrate the influence of a single layer of segregated nanoparticles on color produced. The versatile computational approach presented in this work is useful for engineering synthetic materials with desired colors without laborious trial and error experiments.Comment: 23 Pages, 5 Figures, 1 ToC Figur