Minimal physical requirements for crystal growth self-poisoning

Citation: Whitelam, S., Dahal, Y. R., & Schmit, J. D. (2016). Minimal physical requirements for crystal growth self-poisoning. Journal of Chemical Physics, 144(6), 7. doi:10.1063/1.4941457Self-poisoning is a kinetic trap that can impair or prevent crystal growth in a wide variety of physical settings. Here we use dynamic mean-field theory and computer simulation to argue that poisoning is ubiquitous because its emergence requires only the notion that a molecule can bind in two (or more) ways to a crystal; that those ways are not energetically equivalent; and that the associated binding events occur with sufficiently unequal probability. If these conditions are met then the steady-state growth rate is in general a non-monotonic function of the thermodynamic driving force for crystal growth, which is the characteristic of poisoning. Our results also indicate that relatively small changes of system parameters could be used to induce recovery from poisoning. (C) 2016 AIP Publishing LLC

Dynamics of single polymers under extreme confinement

We study the dynamics of a single chain polymer confined to a two dimensional cell. We introduce a kinetically constrained lattice gas model that preserves the connectivity of the chain, and we use this kinetically constrained model to study the dynamics of the polymer at varying densities through Monte Carlo simulations. Even at densities close to the fully-packed configuration, we find that the monomers comprising the chain manage to diffuse around the box with a root mean square displacement of the order of the box dimensions over time scales for which the overall geometry of the polymer is, nevertheless, largely preserved. To capture this shape persistence, we define the local tangent field and study the two-time tangent-tangent correlation function, which exhibits a glass-like behavior. In both closed and open chains, we observe reptational motion and reshaping through local fingering events which entail global monomer displacement.Comment: 22 pages, 18 figures, slightly extended version to appear in JSTA

Pseudo-one-dimensional nucleation in dilute polymer solutions

Citation: Zhang, L. Y., & Schmit, J. D. (2016). Pseudo-one-dimensional nucleation in dilute polymer solutions. Physical Review E, 93(6), 6. doi:10.1103/PhysRevE.93.060401Pathogenic protein fibrils have been shown in vitro to have nucleation-dependent kinetics despite the fact that one-dimensional structures do not have the size-dependent surface energy responsible for the lag time in classical theory. We present a theory showing that the conformational entropy of the peptide chains creates a free-energy barrier that is analogous to the translational entropy barrier in higher dimensions. We find that the dynamics of polymer rearrangement make it very unlikely for nucleation to succeed along the lowest free-energy trajectory, meaning that most of the nucleation flux avoids the free-energy saddle point. We use these results to construct a three-dimensional model for amyloid nucleation that accounts for conformational entropy, backbone H bonds, and side-chain interactions to compute nucleation rates as a function of concentration

Distinct growth regimes of α-synuclein amyloid elongation

Addition of amyloid seeds to aggregation-prone monomers allows for amyloid fiber growth (elongation) omitting slow nucleation. We here combine Thioflavin T fluorescence (probing formation of amyloids) and solution-state NMR spectroscopy (probing disappearance of monomers) to assess elongation kinetics of the amyloidogenic protein, α-synuclein, for which aggregation is linked to Parkinson\u27s disease. We found that both spectroscopic detection methods give similar kinetic results, which can be fitted by applying double exponential decay functions. When the origin of the two-phase behavior was analyzed by mathematical modeling, parallel paths as well as stop-and-go behavior were excluded as possible explanations. Instead, supported by previous theory, the experimental elongation data reveal distinct kinetic regimes that depend on instantaneous monomer concentration. At low monomer concentrations (toward end of experiments), amyloid growth is limited by conformational changes resulting in β-strand alignments. At the higher monomer concentrations (initial time points of experiments), growth occurs rapidly by incorporating monomers that have not successfully completed the conformational search. The presence of a fast disordered elongation regime at high monomer concentrations agrees with coarse-grained simulations and theory but has not been detected experimentally before. Our results may be related to the wide range of amyloid folds observed

Entanglement model of antibody viscosity

Antibody solutions are typically much more viscous than solutions of globular proteins at equivalent volume fraction. Here we propose that this is due to molecular entanglements that are caused by the elongated shape and intrinsic flexibility of antibody molecules. We present a simple theory in which the antibodies are modeled as linear polymers that can grow via reversible bonds between the antigen binding domains. This mechanism explains the observation that relatively subtle changes to the interparticle interaction can lead to large changes in the viscosity. The theory explains the presence of distinct power law regimes in the concentration dependence of the viscosity as well as the correlation between the viscosity and the charge on the variable domain in our anti-streptavidin IgG1 model system

Diffusion limited reactions in confined environments

We study the effect of confinement on diffusion limited bimolecular reactions within a lattice model where a small number of reactants diffuse amongst a much larger number of inert particles. When the number of inert particles is held constant the rate of the reaction is slow for small reaction volumes due to limited mobility from crowding, and for large reaction volumes due to the reduced concentration of the reactants. The reaction rate proceeds fastest at an intermediate confinement corresponding to volume fraction near 1/2 and 1/3 in two and three dimensions, respectively. We generalize the model to off-lattice systems with hydrodynamic coupling and predict that the optimal reaction rate for monodisperse colloidal systems occurs when the volume fraction is ~0.18. Finally, we discuss the application of our model to bimolecular reactions inside cells as well as the dynamics of confined polymers.Comment: 4 pages, 3 figure