Synthetic ß-sheets mimicking fibrillar and oligomeric structures for evaluation of spectral X-ray scattering technique for biomarker quantification.

BACKGROUND: Archetypical cross-ß spines sharpen the boundary between functional and pathological proteins including ß-amyloid, tau, α-synuclein and transthyretin are linked to many debilitating human neurodegenerative and non-neurodegenerative amyloidoses. An increased focus on development of pathogenic ß-sheet specific fluid and imaging structural biomarkers and conformation-specific monoclonal antibodies in targeted therapies has been recently observed. Identification and quantification of pathogenic oligomers remain challenging for existing neuroimaging modalities. RESULTS: We propose two artificial ß-sheets which can mimic the nanoscopic structural characteristics of pathogenic oligomers and fibrils for evaluating the performance of a label free, X-ray based biomarker detection and quantification technique. Highly similar structure with elliptical cross-section and parallel cross-ß motif is observed among recombinant α-synuclein fibril, Aß-42 fibril and artificial ß-sheet fibrils. We then use these ß-sheet models to assess the performance of spectral small angle X-ray scattering (sSAXS) technique for detecting ß-sheet structures. sSAXS showed quantitatively accurate detection of antiparallel, cross-ß artificial oligomers from a tissue mimicking environment and significant distinction between different oligomer packing densities such as diffuse and dense packings. CONCLUSION: The proposed synthetic ß-sheet models mimicked the nanoscopic structural characteristics of ß-sheets of fibrillar and oligomeric states of Aß and α-synuclein based on the ATR-FTIR and SAXS data. The tunability of ß-sheet proportions and shapes of structural motifs, and the low-cost of these ß-sheet models can become useful test materials for evaluating ß-sheet or amyloid specific biomarkers in a wide range of neurological diseases. By using the proposed synthetic ß-sheet models, our study indicates that the sSAXS has potential to evaluate different stages of ß-sheet-enriched structures including oligomers of pathogenic proteins.

Thermoplastic zwitterionic elastomer with critical antifouling properties.

Thermoplastic elastomers are widely used in the medical industry for advanced medical and healthcare products, helping millions of patients achieve a better quality of life. Yet, microbial contamination and material-associated biofilms on devices remain a critical challenge because it is challenging for currently available materials to provide critical antifouling properties, thermoplasticity, and elastic properties simultaneously. We developed a highly flexible zwitterionic thermoplastic polyurethane with critical antifouling properties. A series of poly((diethanolamine ethyl acetate)-co-poly(tetrahydrofuran)-co-(1,6-diisocyanatohexane)) (PCB-PTHFUs) were synthesized. The PCB-PTHFUs exhibit a breaking strain of more than 400%, a high resistance to fibroblast cells for 24 h, and the excellent ability to prevent biofilm formation for up to three weeks. This study lays a foundation for clarifying the structure-function relationships of zwitterionic polymers. This thermoplastic PCB-PTHFU platform, with its unmatched antifouling properties and high elasticity, has potential for implanted medical devices and a broad spectrum of applications that suffer from biofouling, such as material-associated infection.

On the sensitivity of alginate rheology to composition.

The linear response of alginate-phenyl boronic acid (Alg-PBA) esters shows a universal, composition-independent viscoelastic fluid-like behaviour. Reversible association of alginates governs their rheology at all compositions (viz. at all alginate concentrations and solution pH). However, their high strain behaviour is very sensitive to composition. Tuning composition affords liquids that neck to form filaments capable of being drawn to large elongations without failure. We interpret our data by invoking strain-dependent association and dissociation rates for the alginates. High association rates at high strain result in materials with viscoelastic liquid like behaviour.

Convergent Covalent Organic Framework Thin Sheets as Flexible Supercapacitor Electrodes.

Flexible supercapacitors in modern electronic equipment require light-weight electrodes, which have a high surface area, precisely integrated redox moieties, and mechanically strong flexible free-standing nature. However, the incorporation of the aforementioned properties into a single electrode remains a great task. Herein, we could overcome these challenges by a facile and scalable synthesis of the convergent covalent organic framework (COF) free-standing flexible thin sheets through solid-state molecular baking strategy. Here, redox-active anthraquinone (Dq) and π-electron-rich anthracene (Da) are judiciously selected as two different linkers in a ß-ketoenamine-linked two-dimensional (2D) COF. As a result of precisely integrated anthraquinone moieties, COF thin sheet exhibits redox activity. Meanwhile, π-electron-rich anthracene linker assists to improve the mechanical property of the free-standing thin sheet through the enhancement of noncovalent interaction between crystallites. This binder-free strategy offers the togetherness of crystallinity and flexibility in 2D COF thin sheets. Also, the synthesized porous crystalline convergent COF thin sheets are benefited with crack-free uniform surface and light-weight nature. Further, to demonstrate the practical utility of the material as an electrode in energy-storage systems, we fabricated a solid-state symmetrical flexible COF supercapacitor device using a GRAFOIL peeled carbon tape as the current collector.

Single-Particle Tracking To Probe the Local Environment in Ice-Templated Crosslinked Colloidal Assemblies.

We use single-particle tracking to investigate colloidal dynamics in hybrid assemblies comprising colloids enmeshed in a crosslinked polymer network. These assemblies are prepared using ice templating and are macroporous monolithic structures. We investigate microstructure-property relations in assemblies that appear chemically identical but show qualitatively different mechanical response. Specifically, we contrast elastic assemblies that can recover from large compressive deformations with plastic assemblies that fail on being compressed. Particle tracking provides insights into the microstructural differences that underlie the different mechanical response of elastic and plastic assemblies. Since colloidal motions in these assemblies are sluggish, particle tracking is especially sensitive to imaging artifacts such as stage drift. We demonstrate that the use of wavelet transforms applied to trajectories of probe particles from fluorescence microscopy eliminates stage drift, allowing a spatial resolution of about 2 nm. In elastic and plastic scaffolds, probe particles are surrounded by other particles-thus, their motion is caged. We present mean square displacement and van Hove distributions for particle motions and demonstrate that plastic assemblies are characterized by significantly larger spatial heterogeneity when compared with the elastic sponges. In elastic assemblies, particle diffusivities are peaked around a mean value, whereas in plastic assemblies, there is a wide distribution of diffusivities with no clear peak. Both elastic and plastic assemblies show a frequency independent solid modulus from particle tracking microrheology. Here too, there is a much wider distribution of modulus values for plastic scaffolds as compared to elastic, in contrast to bulk rheological measurements where both assemblies exhibit a similar response. We interpret our results in terms of the spatial distribution of crosslinks in the polymer mesh in the colloidal assemblies.

The Template Determines Whether Chemically Identical Nanoparticle Scaffolds Show Elastic Recovery or Plastic Failure.

Subtle variations in the preparation of ice-templated nanoparticle assemblies yield monoliths that are chemically identical but exhibit qualitatively different mechanical behavior. We ice template aqueous dispersions to prepare macroporous monoliths largely comprising silica nanoparticles held together by a crosslinked polymer mesh. When the polymer is crosslinked in the presence of ice crystals, we obtain an elastic sponge that is capable of recovery after imposition of large compressive strains (up to 80%). If, however, the ice is lyophilized before the polymer is crosslinked, we obtain a plastic monolith that fails even for modest strains (less than 10%). The elastic sponge and the plastic monolith are chemically identical; they have the same organic content, the same ratio of polymer to crosslinker, and the same average crosslink density. Atomic force microscopy (AFM) was used to probe the local mechanical properties of the crosslinked polymer mesh. These measurements indicate that plastic monoliths dissipate significantly more energy and have a larger spatial variation in local mechanical response relative to the elastic sponges. We believe that this behavior might correlate with a wider spatial distribution of crosslinks in plastic scaffolds relative to elastic scaffolds.