Phase Separation and Aggregation of α-Synuclein Diverge at Different Salt Conditions.

The coacervation of alpha-synuclein (αSyn) into cytotoxic oligomers and amyloid fibrils are considered pathological hallmarks of Parkinson's disease. While aggregation is central to amyloid diseases, liquid-liquid phase separation (LLPS) and its interplay with aggregation have gained increasing interest. Previous work shows that factors promoting or inhibiting aggregation have similar effects on LLPS. This study provides a detailed scanning of a wide range of parameters, including protein, salt and crowding concentrations at multiple pH values, revealing different salt dependencies of aggregation and LLPS. The influence of salt on aggregation under crowding conditions follows a non-monotonic pattern, showing increased effects at medium salt concentrations. This behavior can be elucidated through a combination of electrostatic screening and salting-out effects on the intramolecular interactions between the N-terminal and C-terminal regions of αSyn. By contrast, this study finds a monotonic salt dependence of LLPS due to intermolecular interactions. Furthermore, it observes time evolution of the two distinct assembly states, with macroscopic fibrillar-like bundles initially forming at medium salt concentration but subsequently converting into droplets after prolonged incubation. The droplet state is therefore capable of inhibiting aggregation or even dissolving aggregates through heterotypic interactions, thus preventing αSyn from its dynamically arrested state.

Internal sites of actuation and activation in thin elastic films and membranes of finite thickness.

Functionalized thin elastic films and membranes frequently feature internal sites of net forces or stresses. These are, for instance, active sites of actuation, or rigid inclusions in a strained membrane that induce counterstress upon externally imposed deformations. We theoretically analyze the geometry of isotropic, flat, thin, linearly elastic films or membranes of finite thickness, laterally extended to infinity. At the mathematical core of such characterizations are the fundamental solutions for localized force and stress singularities associated with corresponding Green's functions. We derive such solutions in three dimensions and place them into the context of previous two-dimensional calculations. To this end, we consider both no-slip and stress-free conditions at the top and/or bottom surfaces. We provide an understanding for why the fully free-standing thin elastic membrane leads to diverging solutions in most geometries and compare these situations to the truly two-dimensional case. A no-slip support of at least one of the surfaces stabilizes the solution, which illustrates that the divergences in the fully free-standing case are connected to global deformations. Within the aforementioned framework, our results are important for associated theoretical characterizations of thin elastic films, whether supported or free-standing, and of membranes subject to internal or external forces or stresses.

Vortex Pattern Stabilization in Thin Films Resulting from Shear Thickening of Active Suspensions.

The need for structuring on micrometer scales is abundant, for example, in view of phononic applications. We here outline a novel approach based on the phenomenon of active turbulence on the mesoscale. As we demonstrate, a shear-thickening carrier fluid of active microswimmers intrinsically stabilizes regular vortex patterns of otherwise turbulent active suspensions. The fluid self-organizes into a periodically structured nonequilibrium state. Introducing additional passive particles of intermediate size leads to regular spatial organization of these objects. Our approach opens a new path toward functionalization through patterning of thin films and membranes.

Phase Separation and Aggregation of α-Synuclein Diverge at Different Salt Conditions.

The coacervation and structural rearrangement of the protein alpha-synuclein (αSyn) into cytotoxic oligomers and amyloid fibrils are considered pathological hallmarks of Parkinson's disease. While aggregation is recognized as the key element of amyloid diseases, liquid-liquid phase separation (LLPS) and its interplay with aggregation have gained increasing interest. Previous work showed that factors promoting or inhibiting amyloid formation have similar effects on phase separation. Here, we provide a detailed scanning of a wide range of parameters including protein, salt and crowding concentrations at multiple pH values, revealing different salt dependencies of aggregation and phase separation. The influence of salt on aggregation under crowded conditions follows a non-monotonic pattern, showing increased effects at medium salt concentrations. This behavior can be elucidated through a combination of electrostatic screening and salting-out effects on the intramolecular interactions between the N-terminal and C-terminal regions of αSyn. By contrast, we find a monotonic salt dependence of phase separation due to the intermolecular interaction. Furthermore, we observe the time evolution of the two distinct assembly states, with macroscopic fibrillar-like bundles initially forming at medium salt concentration but subsequently converting into droplets after prolonged incubation. The droplet state is therefore capable of inhibiting aggregation or even dissolving the aggregates through a variety of heterotypic interactions, thus preventing αSyn from its dynamically arrested state.

Multiscale X-ray imaging and characterisation of pharmaceutical dosage forms.

A correlative, multiscale imaging methodology for visualising and quantifying the morphology of solid dosage forms by combining ptychographic X-ray computed nanotomography (PXCT) and scanning small- and wide-angle X-ray scattering (S/WAXS) is presented. The methodology presents a workflow for multiscale analysis, where structures are characterised from the nanometre to millimetre regime. Here, the method is demonstrated by characterising a hot-melt extruded, partly crystalline, solid dispersion of carbamazepine in ethyl cellulose. Characterisation of the morphology and solid-state phase of the drug in solid dosage forms is central as this affects the performance of the final formulation. The 3D morphology was visualised at a resolution of 80 nm over an extended volume through PXCT, revealing an oriented structure of crystalline drug domains aligned in the direction of extrusion. Scanning S/WAXS showed that the nanostructure is similar over the cross section of the extruded filament, with minor radial changes in domain sizes and degree of orientation. The polymorphic forms of carbamazepine were qualified with WAXS, showing a heterogeneous distribution of the metastable forms I and II. This demonstrates the methodology for multiscale structural characterization and imaging to enable a better understanding of the relationships between morphology, performance, and processing conditions of solid dosage forms.

Density functional approach to elastic properties of three-dimensional dipole-spring models for magnetic gels.

Magnetic gels are composite materials consisting of a polymer matrix and embedded magnetic particles. Those are mechanically coupled to each other, giving rise to the magnetostrictive effects as well as to a controllable overall elasticity responsive to external magnetic fields. Due to their inherent composite and thereby multiscale nature, a theoretical framework bridging different levels of description is indispensable for understanding the magnetomechanical properties of magnetic gels. In this study, we extend a recently developed density functional approach from two spatial dimensions to more realistic three-dimensional systems. Along these lines, we connect a mesoscopic characterization resolving the discrete structure of the magnetic particles to macroscopic continuum parameters of magnetic gels. In particular, we incorporate the long-range nature of the magnetic dipole-dipole interaction and consider the approximate incompressibility of the embedding media and relative rotations with respect to an external magnetic field breaking rotational symmetry. We then probe the shape of the model system in its reference state, confirming the dependence of magnetostrictive effects on the configuration of the magnetic particles and on the shape of the considered sample. Moreover, calculating the elastic and rotational coefficients on the basis of our mesoscopic approach, we examine how the macroscopic types of behavior are related to the mesoscopic properties. Implications for real systems of random particle configurations are also discussed.

Electromechanical Coupling in Electroactive Polymers - a Visual Analysis of a Third-Order Tensor Field.

Electroactive polymers are frequently used in engineering applications due to their ability to change their shape and properties under the influence of an electric field. This process also works vice versa, such that mechanical deformation of the material induces an electric field in the EAP device. This specific behavior makes such materials highly attractive for the construction of actuators and sensors in various application areas. The electromechanical behaviour of electroactive polymers can be described by a third-order coupling tensor, which represents the sensitivity of mechanical stresses concerning the electric field, i.e., it establishes a relation between a second-order and a first-order tensor field. Due to this coupling tensor's complexity and the lack of meaningful visualization methods for third-order tensors in general, an interpretation of the tensor is rather difficult. Thus, the central engineering research question that this contribution deals with is a deeper understanding of electromechanical coupling by analyzing the third-order coupling tensor with the help of specific visualization methods. Starting with a deviatoric decomposition of the tensor, the multipoles of each deviator are visualized, which allows a first insight into this highly complex third-order tensor. In the present contribution, four examples, including electromechanical coupling, are simulated within a finite element framework and subsequently analyzed using the tensor visualization method.

Stochastic motion under nonlinear friction representing shear thinning.

We study stochastic motion under a nonlinear frictional force that levels off with increasing velocity. Specifically, our frictional force is of the so-called Coulomb-tanh type. At small speed, it increases approximately linearly with velocity, while at large speed, it approaches a constant magnitude, similarly to solid (dry, Coulomb) friction. In one spatial dimension, a formal analogy between the associated Fokker-Planck equation and the Schrödinger equation for a quantum mechanical oscillator in a nonharmonic Pöschl-Teller potential is revealed. Then, the stationary velocity statistics can be treated analytically. From such analytical considerations, we determine associated diffusion coefficients, which we confirm by agent-based simulations. Moreover, from such simulations and from numerically solving the associated Fokker-Planck equation, we find that the spatial distribution function, starting from an initial Gaussian shape, develops tails that appear exponential at intermediate timescales. At small magnitudes of stochastic driving, the velocity distribution resembles the case of linear friction, while at large magnitudes, it rather approaches the case of solid (dry, Coulomb) friction. The same is true for diffusion coefficients. In a certain sense thus interpolating between the two extreme cases of linear friction and solid (dry, Coulomb) friction, our approach should be useful to describe several cases of practical relevance. For instance, a reduced increase in friction with increasing relative speed is typical of shear-thinning behavior. Therefore, driven motion in shear-thinning environments is one specific example to which our description may be applied.

Effect of boundaries on displacements and motion in two-dimensional fluid or elastic films and membranes.

Thin fluid or elastic films and membranes are found in nature and technology, for instance, as confinements of living cells or in loudspeakers. When applying a net force, the resulting flows in an unbounded two-dimensional incompressible low-Reynolds-number fluid or displacements in a two-dimensional linearly elastic solid seem to diverge logarithmically with the distance from the force center, which has led to some debate. Recently, we have demonstrated that such divergences cancel when the total (net) force vanishes. Here, we illustrate that if a net force is present, the boundaries play a prominent role. Already a single no-slip boundary regulates the flow and displacement fields and leads to their decay to leading order inversely in distance from a force center and the boundary. In other words, it is the boundary that stabilizes the system in this situation, unlike the three-dimensional case, where an unbounded medium by itself is able to absorb a net force. We quantify the mobility and displaceability of an inclusion as a function of the distance from the boundary, as well as interactions between different inclusions. In the case of free-slip boundary conditions, a kinked boundary is necessary to achieve stabilization.

Variations in the thermal conductivity of magnetosensitive elastomers by magnetically induced internal restructuring.

Magnetosensitive elastomers respond to external magnetic fields by changing their stiffness and shape. These effects result from interactions among magnetized inclusions that are embedded within an elastic matrix. Strong external magnetic fields induce internal restructuring, for example the formation of chain-like aggregates. However, such reconfigurations affect not only the overall mechanical properties of the elastomers but also the transport through such systems. We concentrate here on the transport of heat, that is thermal conductivity. For flat, thin model systems representing thin films or membranes and modeled by bead-spring discretizations, we evaluate the internal restructuring in response to magnetization of the particles. For each resulting configuration, we evaluate the associated thermal conductivity. We analyze the changes in heat transport as a function of the strength of magnetization, particle number, density of magnetizable particles (at fixed overall particle number), and aspect ratio of the system. We observe that varying any one of these parameters can induce pronounced changes in the bulk thermal conductivity. Our results motivate future experimental and theoretical studies of systems with magnetically tunable thermal but also electric conductivity-both of which have only rarely been addressed so far.

When low-order expansions fail and all higher-order contributions matter-basic example of the mean squared displacement for Brownian motion.

Hardly any theoretically formulated realistic problem can be solved exactly. Therefore, as a standard, we resort to approximations. In this context, expansions play a major role. We are used to relying on lowest-order expansions and confining our point of view accordingly. However, one should always bear in mind that such considerations may fail at some point. Here, we address a very common example situation, namely, the motion of a Brownian particle. We know that the associated mean-squared displacement in the long term increases linearly in time. Yet, when we take the Fokker-Planck approach in combination with a low-order expansion, the direct route towards this result fails. That is, in the expansion the term linear in time vanishes. Instead, the treatment requires consideration of all higher-order contributions. Together, they restore the linear increase in time. In this way, we stress that care is always mandatory when resorting to low-order expansions, and we present in a traceable way a route to solving the considered problem.

Statistics for an object actively driven by spontaneous symmetry breaking into reversible directions.

Propulsion of otherwise passive objects is achieved by mechanisms of active driving. We concentrate on cases in which the direction of active drive is subject to spontaneous symmetry breaking. In our case, this direction will be maintained until a large enough impulse by an additional stochastic force reverses it. Examples may be provided by self-propelled droplets, gliding bacteria stochastically reversing their propulsion direction, or nonpolar vibrated hoppers. The magnitude of active forcing is regarded as constant, and we include the effect of inertial contributions. Interestingly, this situation can formally be mapped to stochastic motion under (dry, solid) Coulomb friction, however, with a negative friction parameter. Diffusion coefficients are calculated by formal mapping to the situation of a quantum-mechanical harmonic oscillator exposed to an additional repulsive delta-potential. Results comprise a ditched or double-peaked velocity distribution and spatial statistics showing outward propagating maxima when starting from initially concentrated arrangements.

Circular motion subject to external alignment under active driving: Nonlinear dynamics and the circle map.

Hardly any real self-propelling or actively driven object is perfect. Thus, undisturbed motion will generally not follow straight lines but rather bent or circular trajectories. We here address self-propelled or actively driven objects that move in discrete steps and additionally tend to migrate towards a certain direction by discrete angular adjustment. Overreaction in the angular alignment is possible. This competition implies pronounced nonlinear dynamics including period doubling and chaotic behavior in a broad parameter regime. Such behavior directly affects the appearance of the trajectories. Furthermore, we address collective motion and effects of spatial self-concentration.

Imaging of retina cellular and subcellular structures using ptychographic hard X-ray tomography.

Ptychographic hard X-ray computed tomography (PXCT) is a recent method allowing imaging with quantitative electron-density contrast. Here, we imaged, at cryogenic temperature and without sectioning, cellular and subcellular structures of a chemically fixed and stained wild-type mouse retina, including axons and synapses, with complete isotropic 3D information over tens of microns. Comparison with tomograms of degenerative retina from a mouse model of retinitis pigmentosa illustrates the potential of this method for analyzing disease processes like neurodegeneration at sub-200 nm resolution. As a non-destructive imaging method, PXCT is very suitable for correlative imaging. Within the outer plexiform layer containing the photoreceptor synapses, we identified somatic synapses. We used a small region inside the X-ray-imaged sample for further high-resolution focused ion beam/scanning electron microscope tomography. The subcellular structures of synapses obtained with the X-ray technique matched the electron microscopy data, demonstrating that PXCT is a powerful scanning method for tissue volumes of more than 60 cells and sensitive enough for identification of regions as small as 200 nm, which remain available for further structural and biochemical investigations.

Stimuli-responsive twist actuators made from soft elastic composite materials-linking mesoscopic and macroscopic descriptions.

Very recently, the construction of twist actuators from magnetorheological gels and elastomers has been suggested. These materials consist of magnetizable colloidal particles embedded in a soft elastic polymeric environment. The twist actuation is enabled by a net chirality of the internal particle arrangement. Upon magnetization by a homogeneous external magnetic field, the systems feature an overall torsional deformation around the magnetization direction. Starting from a discrete minimal mesoscopic model setup, we work toward a macroscopic characterization. The two scales are linked by identifying expressions for the macroscopic system parameters as functions of the mesoscopic model parameters. In this way, the observed behavior of a macroscopic system can, in principle, be mapped to and illustratively be understood from an appropriate mesoscopic picture. Our results apply equally well to corresponding soft electrorheological gels and elastomers.

Sparse ab initio x-ray transmission spectrotomography for nanoscopic compositional analysis of functional materials.

The performance of functional materials is either driven or limited by nanoscopic heterogeneities distributed throughout the material's volume. To better our understanding of these materials, we need characterization tools that allow us to determine the nature and distribution of these heterogeneities in their native geometry in 3D. Here, we introduce a method based on x-ray near-edge spectroscopy, ptychographic x-ray computed nanotomography, and sparsity techniques. The method allows the acquisition of quantitative multimodal tomograms of representative sample volumes at sub-30 nm half-period spatial resolution within practical acquisition times, which enables local structure refinements in complex geometries. To demonstrate the method's capabilities, we investigated the transformation of vanadium phosphorus oxide catalysts with industrial use. We observe changes from the micrometer to the atomic level and the formation of a location-specific defect so far only theorized. These results led to a reevaluation of these catalysts used in the production of plastics.

Structural color from solid-state polymerization-induced phase separation.

Structural colors are produced by wavelength-dependent scattering of light from nanostructures. While living organisms often exploit phase separation to directly assemble structurally colored materials from macromolecules, synthetic structural colors are typically produced in a two-step process involving the sequential synthesis and assembly of building blocks. Phase separation is attractive for its simplicity, but applications are limited due to a lack of robust methods for its control. A central challenge is to arrest phase separation at the desired length scale. Here, we show that solid-state polymerization-induced phase separation can produce stable structures at optical length scales. In this process, a polymeric solid is swollen and softened with a second monomer. During its polymerization, the two polymers become immiscible and phase separate. As free monomer is depleted, the host matrix resolidifies and arrests coarsening. The resulting polymeric composites have a blue or white appearance. We compare these biomimetic nanostructures to those in structurally-colored feather barbs, and demonstrate the flexibility of this approach by producing structural color in filaments and large sheets.

Dynamical Crystallites of Active Chiral Particles.

One of the intrinsic characteristics of far-from-equilibrium systems is the nonrelaxational nature of the system dynamics, which leads to novel properties that cannot be understood and described by conventional pathways based on thermodynamic potentials. Of particular interest are the formation and evolution of ordered patterns composed of active particles that exhibit collective behavior. Here we examine such a type of nonpotential active system, focusing on effects of coupling and competition between chiral particle self-propulsion and self-spinning. It leads to the transition between three bulk dynamical regimes dominated by collective translative motion, spinning-induced structural arrest, and dynamical frustration. In addition, a persistently dynamical state of self-rotating crystallites is identified as a result of a localized-delocalized transition induced by the crystal-melt interface. The mechanism for the breaking of localized bulk states can also be utilized to achieve self-shearing or self-flow of active crystalline layers.

Nanoscale crystal grain characterization via linear polarization X-ray ptychography.

X-ray linear dichroism and X-ray birefringence microscopy are yet to be fully utilized as instruments in the microstructural characterization of crystalline materials. Here, we demonstrate analyser-free X-ray linear dichroism microscopy using spectroscopic hard X-ray ptychography. First experiments enabled a spectroscopic and microstructural characterisation of polycrystalline vanadium pentoxide on the nanoscale, outside of diffraction-contrast based methods.

Towards an analytical description of active microswimmers in clean and in surfactant-covered drops.

Geometric confinements are frequently encountered in the biological world and strongly affect the stability, topology, and transport properties of active suspensions in viscous flow. Based on a far-field analytical model, the low-Reynolds-number locomotion of a self-propelled microswimmer moving inside a clean viscous drop or a drop covered with a homogeneously distributed surfactant, is theoretically examined. The interfacial viscous stresses induced by the surfactant are described by the well-established Boussinesq-Scriven constitutive rheological model. Moreover, the active agent is represented by a force dipole and the resulting fluid-mediated hydrodynamic couplings between the swimmer and the confining drop are investigated. We find that the presence of the surfactant significantly alters the dynamics of the encapsulated swimmer by enhancing its reorientation. Exact solutions for the velocity images for the Stokeslet and dipolar flow singularities inside the drop are introduced and expressed in terms of infinite series of harmonic components. Our results offer useful insights into guiding principles for the control of confined active matter systems and support the objective of utilizing synthetic microswimmers to drive drops for targeted drug delivery applications.