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Polymer nanocomposites (PNCs) have found their way into our everyday lives in a long list of applications, including airplane parts and car tires. This is due to their unique properties of combining the strengths of their constituents – elasticity and stiffness – while mitigating their weaknesses – softness and brittleness. In the past few decades, they have generated more interest due to the discovery that the PNCs’ optical, electrical, and a host of other properties can be tuned for specific use by controlling the assembly and dispersion of nanoparticles (NPs) within the host polymer matrix. The grafting of some of the matrix chains onto the surface of the NPs not only improves NP miscibility but also grants an additional handle tocontrol the self-assembly of NPs. However, at present, there remains many open questions in the field of these novel PNCs. For instance, it is commonly believed that long enough matrix polymers of length P will spontaneously dewet a chemically identical polymer layer, comprised of sufficient chains of length N , end-grafted to a flat surface (”brush”). This entropically driven idea is frequently used to explain experiments in which 10-20 nm diameter polymer-grafted NPs are observed to phase separate from homopolymer matrices for P/N⪆4. At lower grafting densities, these entropic effects are also thought to underpin the self-assembly of grafted NPs into a diverse set of structures. To explore the validity of this picture, a two-pronged approach is used in this thesis, exploring such systems from both a single NP and a multi-NP point of view in order to find novel methods for understanding and controlling NP dispersion in polymers. In each of the chapters, we employ coarse-grained Molecular Dynamics (MD) simulations to understand the self-assembly and dispersion behavior in PNCs, with the experimental analog being primarily polystyrene (PS) grafted silica NPs in PS matrices. We start by investigating the entropic effects of P/N on the brush of a single grafted NP, taking advantage of an indirect umbrella sampling method (INDUS) to quantify matrix density fluctuations. This method essentially makes use of an external biasing potential to mimic the dewetting of the brush. We find for the first time that entropic P/N effects can be identified at the single NP level and is primarily surface driven. INDUS is later extended to two-body and many-body NP systems, to understand the role of NP surfactantcy in the self-assembly of grafted NPs and create free-energy profiles for a range of inter-NP separations. Finally, results from a comprehensive series of large-scale multi-NP simulations, where we consider NPs in the ≈ 5nm and ≈ 10nm size range. For the smaller NPs, we find no evidence of phase separation even for P/N = 10 in the absence of attractions. Instead, we discover that we are able to recreate most of the experimentally observed structures when allthe polymer chain monomers are equally attractive to each other but repel the NPs. Only when the NPs are in the ≈ 10nm size range that we are able to access the phase separated morphologies. Our results thus imply that experimental situations where the grafting density is low are dominated by the surfactancy of the NPs, which is driven by the chemical mismatch between the inorganic core and the organic ligands (the graft and free chains are chemically identical). Entropic effects, i.e. the translational entropy of the NPs and the matrix, the entropy of mixing of the grafts and the matrix, and the conformational entropy of the chains appear to thus play a second order effect even in the context of these model systems. Each of these insights provides details around controlling the organization and assembly of NPs in polymers for the purpose of improving their mechanical properties, all while changing the way in which the material is designed.

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Nuclear Engineering, 1982. / MICROFICHE COPY AVAILABLE IN ARCHIVES AND SCIENCE. / Bibliography: leaves 144-147. / by Benito De Celis. / Ph.D.

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Amyloids are highly ordered cross-β sheet aggregates that are associated with many diseases such as Alzheimer‟s, type II diabetes and prion diseases. Recently a progress has been made in structure elucidation, environmental effects and thermodynamic properties of amyloid aggregates. However, detailed understanding of how mutation, packing polymorphism and small organic molecules influence amyloid structure and dynamics is still lacking. Atomistic modeling of these phenomena with molecular dynamics (MD) simulations holds a great promise to bridge this gap. This Thesis describes the results of MD simulations, which provide insight into the effects of mutation, packing polymorphism and molecular inhibitors on amyloid peptides aggregation. Chapter 1 discusses the structure of amyloid peptides, diseases associated with amyloid aggregation, mechanism of aggregation and strategies to treat amyloid diseases. Chapter 2 describes the basic principles of molecular dynamic simulation and methods of trajectory analysis used in the Thesis. Chapter 3 presents the results of the study of several all-atom molecular dynamics simulations with explicit solvent, starting from the crystalline fragments of two to ten monomers each. Three different hexapeptides and their analogs produced with single glycine replacement were investigated to study the structural stability, aggregation behavior and thermodynamics of the amyloid oligomers. Chapter 4 presents multiple molecular dynamics (MD) simulation of a pair polymorphic form of five short segments of amyloid peptide. Chapter 5 describes MD study of single-layer oligomers of the full-length insulin with a goal to identify the structural elements that are important for insulin amyloid stability, and to suggest single glycine mutants that may improve formulation. Chapter 6 presents the investigation of the mechanism of the interaction of polyphenols molecules with the protofibrils formed by an amyloidogenic hexapeptide fragment (VQIVYK) of Tau peptide by molecular dynamics iii simulations in explicit solvent. We analyzed the trajectories of the large (7×4) aggregate with and without the polyphenols. Our MD simulations for both the short and full length amyloids revealed adding strands enhances the internal stability of wildtype aggregates. The degree of structural similarity between the oligomers in simulation and the fibril models constructed based on experimental data may explain why adding oligomers shortens the experimentally observed nucleation lag phase of amyloid aggregation. The MM-PBSA free energy calculation revealed nonpolar components of the free energy is more favorable while electrostatic solvation is unfavorable for the sheet to sheet interaction. This explains the acceleration of aggregation by adding nonpolar co-solvents (methanol, trifluoroethanol, and hexafluoroisopropanol). Free energy decomposition shows residues situated at the interface were found to make favorable contribution to the peptide -peptide association. The results from the simulations might provide both the valuable insight for amyloid aggregation as well as assist in inhibitor design efforts. First, the simulation of the single glycine mutants at the steric zipper of the short segments of various pathological peptides indicates the intersheet steric zipper is important for amyloid stability. Mutation of the side chains at the dry steric zipper disrupts the sheet to sheet packing, making the aggregation unstable. Thus, designing new peptidomimetic inhibitors able to prevent the fibril formation based on the steric zipper motif of the oligomers, similar to the ones examined in this study may become a viable therapeutic strategy. The various steric zipper microcrystal structures of short amyloid segments could be used as a template to design aggregation inhibitor that can block growth of the aggregates. Modification of the steric zipper structure (structure based design) with a single amino acid changes, shuffling the sequences, N- methylation of peptide amide bonds to suppress hydrogen iv bonding ability of NH groups or replacement with D amino acid sequence that interact with the parent steric zipper could be used in computational search for the new inhibitors. Second, the polyphenols were found to interact with performed oligomer through hydrogen bonding and induce conformational change creating an altered aggregate. The conformational change disrupts the intermolecular amyloid contact remodeling the amyloid aggregate. The recently reported microcrystal structure of short segments of amyloid peptides with small organic molecules could serve as a pharamcophore for virtual screening of aggregation inhibitor using combined docking and MD simulation with possible enhancement of lead enrichment. Finally, our MD simulation of short segments of amyloids with steric zipper polymorphism showed the stability depends on both sequence and packing arrangements. The hydrophilic polar GNNQQNY and NNQNTF with interface containing large polar and/or aromatic side chains (Q/N) are more stable than steric zipper interfaces made of small or hydrophobic residues (SSTNVG, VQIVYK, and MVGGVV). The larger sheet to sheet interface of the dry steric zipper through polar Q/N rich side chains was found to holds the sheets together better than non Q/N rich short amyloid segments. The packing polymorphism could influence the structure based design of aggregation inhibitor and a combination of different aggregation inhibitors might be required to bind to various morphologic forms of the amyloid peptides.

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We employ molecular dynamics simulations to investigate the evaporation process of nanosized droplets adsorbed on a substrate. Beads interacting with each other via Lennard-Jones (LJ) potentials are used to construct the simulation systems. The solid substrate contains 6 layers of beads forming a face-centered-cubic lattice. The bottom 3 layers are held rigid while the rest is kept at a constant temperature with a Langevin thermostat. A liquid droplet, consisting of LJ beads as well, is placed on top of the substrate. An appropriate amount of vapor beads are also supplied to the simulation box to help establish liquid-vapor equilibrium. To ensure adsorption, a stronger attraction is rendered between the droplet and a circular patch of 3 layers of beads at the center of the substrate surface while the rest of the substrate is made non-sticky for the fluid beads. During equilibration, the droplet and vapor are maintained at the same temperature as the thermalized substrate. After relaxation, the droplet adheres to the attractive patch as expected. Then a deletion zone is introduced into the top part of the vapor region. Fluid beads in this zone are removed at a given rate. To ensure that the evaporation dynamics and kinetics are properly captured, only the thermalized substrate is kept at the constant temperature during droplet evaporation. To carry out steady-state evaporation, the removed beads are reintroduced into a channel through the substrate and right below the droplet's center. These beads are then supplied to the droplet, compensating for the evaporation loss at the droplet surface. When the evaporation rate and the insertion rate are balanced, the system enters a steady state with the droplet undergoing continuous evaporation and its contact line pinned at the boundary of the attractive patch on the substrate. A one-to-one correspondence is found between the evaporation rate and the total number of fluid beads in the simulation box, as well as the contact angle of the droplet. Using this steady nonequilibrium system, we have mapped out the flow, temperature, and density fields inside and around the evaporating droplet as well as the local evaporation flux along the droplet surface with unprecedented resolutions. The results are used to test the existing theories on sessile droplet evaporation. / Master of Science / Droplet evaporation is a widespread natural phenomenon with numerous applications across various fields. While there has been extensive research on droplet evaporation, it remains a challenge to characterize the interior of the droplet and the local evaporation behavior on the droplet surface. Here we employ molecular dynamics (MD) simulation to model a nanosized droplet adsorbed on a substrate, which evaporates continuously while maintains a constant shape. This is realized by supplying the evaporated fluid back to the bottom of the droplet through an in-silico approach. Such a steady-evaporation system allows us to accurately map out the internal capillary flow of the evaporating droplet with a pinned contact line, where the droplet, vapor, and substrate meet. We find that local evaporation occurs faster near the contact line than at the apex of the droplet.