Particles with directional interactions are promising building blocks for new functional materials and may serve as models for biological structures 1,2,3 . Mutually attractive nanoparticles that are deformable due to flexible surface groups, for example, may spontaneously order themselves into strings, sheets and large vesicles 4,5,6 . Furthermore, anisotropic colloids with attractive patches can self-assemble into open lattices and colloidal equivalents of molecules and micelles 7,8,9 . However, model systems that combine mutual attraction, anisotropy, and deformability have-to the best of our knowledge-not been realized. Here, we synthesize colloidal particles that combine these three characteristics and obtain selfassembled microcapsules. We propose that mutual attraction and deformability induce directional interactions via colloidal bond hybridization. Our particles contain both mutually attractive and repulsive surface groups that are flexible. Analogous to the simplest chemical bond, where two isotropic orbitals hybridize into the molecular orbital of H 2 , these flexible groups redistribute upon binding. Via colloidal bond hybridization, isotropic spheres self-assemble into planar monolayers, while anisotropic snowman-like particles self-assemble into hollow monolayer microcapsules. A modest change of the building blocks thus results in a significant leap in the complexity of the self-assembled structures. In other words, 1 arXiv:1503.00552v3 [cond-mat.soft] 18 Jul 2016 these relatively simple building blocks self-assemble into dramatically more complex structures than similar particles that are isotropic or non-deformable.For self-assembly of nanoparticles, deformability and mutual attraction have recently been combined by grafting flexible polymers onto the surface of mutually attractive particles. This results in isotropic clusters 10 , and selfassembled strings, sheets, and large vesicles 4,5 . For micrometre-sized colloids, on the other hand, coupling mutual attraction and anisotropy leads to patchy particles. Attractive domains, or patches, have induced self-assembly into open lattices and colloidal equivalents of molecules and micelles 7,8,9 . Here, we combine the three properties mutual attraction, anisotropy and deformability, by synthesizing snowman-like particles that consist of a deformable core and a non-deformable lobe or protrusion. In the first part of this letter, mutual attraction is combined with deformability, resulting in anisotropic or directional interactions as flexible surface groups redistribute upon binding (Fig. 1e). This process is analogous to bond hybridization in quantum chemistry. When two hydrogen atoms bind and form H 2 , for example, the electrons around each atom redistribute, i.e. two isotropic orbitals hybridize into the molecular orbitals of H 2 . Similarly, when mutually attractive, deformable particles bind, flexible surface groups redistribute, resulting in directional interactions. We refer to this effect as colloidal bond hybridization. We observe ...

We performed replica exchange molecular dynamics and forward flux sampling simulations of hexapeptide VQIINK and VQIVYK systems, also known as, respectively, fragments PHF6* and PHF6 from the tau protein. Being a part of the microtubule binding region, these fragments are known to be aggregation prone, and at least one of them is a prerequisite for fibril formation of the tau protein. Using a coarse-grained force field, we establish the phase behavior of both fragments, and investigate the nucleation kinetics for the conversion into a β-sheet fibril. As the conversion is, in principle, a reversible process, we predict the rate constants for both the fibril formation and melting, and examine the corresponding mechanisms. Our simulations indicate that, while both fragments form disordered aggregates, only PHF6 is able to form β-sheet fibrils. This observation provides a possible explanation for the lack of available steric zipper crystal structures for PHF6*.

Amyloid fibril formation is believed to be a nucleation-controlled process. Depending on the nature of peptide sequence, fibril nucleation can occur in one step, straight from a dilute solution, or in multiple steps via oligomers or disordered aggregates. What determines this process is poorly understood. Since the fibril formation kinetics is driven by thermodynamic forces, knowledge of the phase behavior is crucial. Here, we investigated the phase behavior of three short peptide sequences of varying side-chain hydrophobicity. Replica exchange molecular dynamics simulations of a mid-resolution model indicate that the weakly hydrophobic peptide forms fibrils directly from solution, whereas the most hydrophobic peptide forms a dense liquid phase before crystallizing into ordered fibrils at low temperatures. For the medium hydrophobic peptide we found evidence of a novel additional transition to a liquid phase consisting of clusters of aligned peptides, implying a three-step nucleation process. We tested the robustness of this prediction by applying Wertheim's theory and statistical associating fluid theory to a hard-sphere model dressed with isotropic and anisotropic attractions. We found that the ratio of interaction strengths strongly affects the phase behavior, and under certain conditions indeed gives rise to a stable polymerized liquid phase. The peptide clusters in the associated liquid tend to be slow and long-lived, which may give the oligomer droplet more time to act as a toxic oligomer, before turning into a fibril.

The primary nucleation step in amyloid fibril formation can, depending on the nature of peptide sequence, occur in one step, straight from a dilute solution, or in multiple steps, via oligomers or disordered aggregates. The precise kinetic pathways of these processes are poorly understood. Employing forward flux sampling and a midresolution coarse-grained force field, we analyzed the reactive pathways from the solvated state to the fibril nucleus for a system of 12 amyloidogenic peptides. In line with previous work, increasing the overall side-chain hydrophobicity switches the fibrillization mechanism from one- to two-step nucleation. Overall, in this mechanism, peptides first form dimers and trimers, which then grow into a β-sheet. This sheet serves as a template for nucleation of additional β sheets until the fibril nucleus is fully formed. Our simulations indicate that the presence of the recently predicted polymerized phase in the nucleation pathway of intermediately hydrophobic peptides slows down the dynamics of fibril formation considerably, which may influence the time scale on which toxic early oligomers exist. The structure of the amyloid fibrils was found to be strongly dependent on the relative hydrophobic strength of side chains along the sequence: β sheets in the fibril are oriented such that a core of the relative strongest hydrophobic residues is formed along the fibril axis.

We report a numerical study of a simple, modified Asakura-Oosawa model for nanoparticles that are isotropically grafted with polymer chains. We perform canonical and grand-canonical Monte Carlo simulations to establish a qualitative morphology diagram, as well as quantitative phase diagrams. The morphology diagram qualitatively reproduces experimental observations and theoretical approaches employing more complex models. In addition, we establish the transition lines for a microphase separation and show that the phase behavior saturates for larger polymer sizes. An analytical treatment on the level of the second virial coefficient indicates that this saturation effect is caused by less effective shielding of nanoparticles by longer polymers. Our simple model enables large-scale particle-based simulations of self-assembly of polymer-coated particles.