Amyloidogenesis of SARS-CoV-2 Spike Protein

SARS-CoV-2 infection is associated with a surprising number of morbidities. Uncanny similarities with amyloid-disease associated blood coagulation and fibrinolytic disturbances together with neurologic and cardiac problems led us to investigate the amyloidogenicity of the SARS-CoV-2 Spike protein (S-protein). Amyloid fibril assays of peptide library mixtures and theoretical predictions identified seven amyloidogenic sequences within the S-protein. All seven peptides in isolation formed aggregates during incubation at 37°C. Three 20-amino acid long synthetic Spike peptides (sequence 191-210, 599-618, 1165-1184) fulfilled three amyloid fibril criteria: nucleation dependent polymerization kinetics by ThT, Congo red positivity and ultrastructural fibrillar morphology. Full-length folded S-protein did not form amyloid fibrils, but amyloid-like fibrils with evident branching were formed during 24 hours of S-protein co-incubation with the protease neutrophil elastase (NE) in vitro. NE efficiently cleaved S-protein rendering exposure of amyloidogenic segments and accumulation of the peptide 193-202, part of the most amyloidogenic synthetic Spike peptide. NE is overexpressed at inflamed sites of viral infection and at vaccine injection sites. Our data propose a molecular mechanism for amyloidogenesis of SARS-CoV-2 S-protein in humans facilitated by endoproteolysis. The potential implications of S-protein amyloidogenesis in COVID-19 disease associated pathogenesis and consequences following S-protein based vaccines should be addressed in understanding the disease, long COVID-19, and vaccine side effects.

Morphology, Rheological and Mechanical Properties of Isotropic and Anisotropic PP/rPET/GnP Nanocomposite Samples

The effect of graphene nanoplatelets (GnPs) on the morphology, rheological, and mechanical properties of isotropic and anisotropic polypropylene (PP)/recycled polyethylene terephthalate (rPET)-based nanocomposite are reported. All the samples were prepared by melt mixing. PP/rPET and PP/rPET/GnP isotropic sheets were prepared by compression molding, whereas the anisotropic fibers were spun using a drawing module of a capillary viscometer. The results obtained showed that the viscosity of the blend is reduced by the presence of GnP due to the lubricating effect of the graphene platelets. However, the Cox–Merz rule is not respected. Compared to the PP/rPET blend, the GnP led to a slight increase in the elastic modulus. However, it causes a slight decrease in elongation at break. Morphological analysis revealed a poor adhesion between the PP and PET phases. Moreover, GnPs distribute around the droplets of the PET phase with a honey-like appearance. Finally, the effect of the orientation on both systems gives rise not only to fibers with higher modulus values, but also with high deformability and a fibrillar morphology of the dispersed PET phase. A fragile-ductile transition driven by the orientation was observed in both systems.

β-Barrels and Amyloids: Structural Transitions, Biological Functions, and Pathogenesis

Insoluble protein aggregates with fibrillar morphology called amyloids and β-barrel proteins both share a β-sheet-rich structure. Correctly folded β-barrel proteins can not only function in monomeric (dimeric) form, but also tend to interact with one another—followed, in several cases, by formation of higher order oligomers or even aggregates. In recent years, findings proving that β-barrel proteins can adopt cross-β amyloid folds have emerged. Different β-barrel proteins were shown to form amyloid fibrils in vitro. The formation of functional amyloids in vivo by β-barrel proteins for which the amyloid state is native was also discovered. In particular, several prokaryotic and eukaryotic proteins with β-barrel domains were demonstrated to form amyloids in vivo, where they participate in interspecies interactions and nutrient storage, respectively. According to recent observations, despite the variety of primary structures of amyloid-forming proteins, most of them can adopt a conformational state with the β-barrel topology. This state can be intermediate on the pathway of fibrillogenesis (“on-pathway state”), or can be formed as a result of an alternative assembly of partially unfolded monomers (“off-pathway state”). The β-barrel oligomers formed by amyloid proteins possess toxicity, and are likely to be involved in the development of amyloidoses, thus representing promising targets for potential therapy of these incurable diseases. Considering rapidly growing discoveries of the amyloid-forming β-barrels, we may suggest that their real number and diversity of functions are significantly higher than identified to date, and represent only “the tip of the iceberg”. Here, we summarize the data on the amyloid-forming β-barrel proteins, their physicochemical properties, and their biological functions, and discuss probable means and consequences of the amyloidogenesis of these proteins, along with structural relationships between these two widespread types of β-folds.

Amyloids as Building Blocks for Macroscopic Functional Materials: Designs, Applications and Challenges

Amyloids are self-assembled protein aggregates that take cross-β fibrillar morphology. Although some amyloid proteins are best known for their association with Alzheimer’s and Parkinson’s disease, many other amyloids are found across diverse organisms, from bacteria to humans, and they play vital functional roles. The rigidity, chemical stability, high aspect ratio, and sequence programmability of amyloid fibrils have made them attractive candidates for functional materials with applications in environmental sciences, material engineering, and translational medicines. This review focuses on recent advances in fabricating various types of macroscopic functional amyloid materials. We discuss different design strategies for the fabrication of amyloid hydrogels, high-strength materials, composite materials, responsive materials, extracellular matrix mimics, conductive materials, and catalytic materials.

Small, Seeding-Competent Huntingtin Fibrils Are Prominent Aggregate Species in Brains of zQ175 Huntington’s Disease Knock-in Mice

The deposition of mutant huntingtin (mHTT) protein aggregates in neurons of patients is a pathological hallmark of Huntington’s disease (HD). Previous investigations in cell-free and cell-based disease models showed mHTT exon-1 (mHTTex1) fragments with pathogenic polyglutamine (polyQ) tracts (>40 glutamines) to self-assemble into highly stable, β-sheet-rich protein aggregates with a fibrillar morphology. HD knock-in mouse models have not been extensively studied with regard to mHTT aggregation. They endogenously produce full-length mHTT with a pathogenic polyQ tract as well as mHTTex1 fragments. Here, we demonstrate that seeding-competent, fibrillar mHTT aggregates can be readily detected in brains of zQ175 knock-in HD mice. To do this, we applied a highly sensitive FRET-based protein amplification assay that is capable of detecting seeding-competent mHTT aggregate species down to the femtomolar range. Furthermore, we show that fibrillar structures with an average length of ∼200 nm can be enriched with aggregate-specific mouse and human antibodies from zQ175 mouse brain extracts through immunoprecipitations, confirming that such structures are formed in vivo. Together these studies indicate that small, fibrillar, seeding-competent mHTT structures are prominent aggregate species in brains of zQ175 mice.

Nanoporous Crystalline Composite Aerogels with Reduced Graphene Oxide

High-porosity monolithic composite aerogels of syndiotactic polystyrene (sPS) and poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) containing reduced graphene oxide (r-GO) were prepared and characterized. The composite aerogels obtained by supercritical carbon dioxide (scCO2) extraction of sPS/r-GO and PPO/r-GO gels were characterized by a fibrillar morphology, which ensured good handling properties. The polymer nanoporous crystalline phases obtained within the aerogels led to high surface areas with values up to 440 m2 g−1. The role of r-GO in aerogels was studied in terms of catalytic activity by exploring the oxidation capacity of composite PPO and sPS aerogels toward benzyl alcohol in diluted aqueous solutions. The results showed that, unlike sPS/r-GO aerogels, PPO/r-GO aerogels were capable of absorbing benzyl alcohol from the diluted solutions, and that oxidation of c.a. 50% of the sorbed benzyl alcohol molecules into benzoic acid occurred.

Bispicolyamine-Based Supramolecular Polymeric Gels Induced by Distinct Different Driving Forces with and Without Zn2+

Metal-coordination polymeric gels are interesting areas as organic/inorganic hybrid supramolecular materials. The bispicolylamine (BPA) based gelator (1) showed excellent gelation with typical fibrillar morphology in acetonitrile. Upon complexing 1 with Zn2+, complexes ([1 + Zn + ACN]2+ and [1 + zinc trifluoromethanesulfonate (ZnOTf)]+) with four coordination numbers were formed, which determine the gel structure significantly. A gel-sol transition was induced, driven by the ratio of the two metal complexes produced. Through nuclear magnetic resonance analysis, the driving forces in the gel formation (i.e., hydrogen-bonding and π–π stacking) were observed in detail. In the absence and the presence of Zn2+, the intermolecular hydrogen-bonds and π–π stacking were the primary driving forces in the gel formation, respectively. In addition, the supramolecular gels exhibited a monolayer lamellar structure irrespective of Zn2+. Conclusively, the gels’ elasticity and viscosity reduced in the presence of Zn2+.

APPLICATION OF SODIUM TITANATE BASED NANOMATERIALS FOR DYE ADSORPTION

The application of sodium titanium-based nanomaterials for the adsorption of dyes deserves to be invested by an innovative and low-cost technique. Also, contamination of effluents by used dyes can cause damage and public health due to their toxicity and recalcitrance. So, an end of environmental impact impacted by these effluents, it is necessary or the development of new technologies of removal. An alternative to remedy this problem is found in the application of the adsorption technique through the use of sodium titanium nanomaterials. These factors do not have surface areas, spaces between and charge transfer rates of efficient interfaces, or what significantly increases the adsorbents. Thus, the present work aimed to synthesize sodium titanium nanomaterials and to investigate their use for the removal of dyes or gum from the aqueous medium. The materials were synthesized using the hydrothermal method, without the use of a structured guide, using titanium dioxide as the starting material in the alkaline medium (10M NaOH). These materials were studied, using their use in the removal of organic pollutants in aqueous medium, where it verified the formation of fibrillar morphology for all the materials used. Through the X-ray diffraction technique, it was confirmed the establishment of four crystallographic phases of lamellar titanates, predominantly, of disodium titanate, with monoclinic symmetry. In short, the results proved that there was a formation of titanate nanomaterials. Tests to remove methylene blue are promising for the adsorptive activity of the captured materials concerning the starting oxide, removing up to 81% of the dye in 30 min. Titanium nanomaterials are efficient to remedy aquatic ecosystems contaminated by this organic pollutant; in addition, the collected data become a reference for future studies.

Nanofibrillar Green Composites of Polylactide/Polyhydroxyalkanoate Produced in Situ Due to Shear Induced Crystallization

This study addresses the new concept of in situ inducing fibrillar morphology (micro or nanofibrils) of a minority component based on the simultaneous occurrence of orientation and shear induced crystallization of polymer fibers directly at the stage of extrusion in a single step. This possibility is demonstrated by using two entirely bio-sourced polymers: polylactide (PLA) and polyhydroxyalkanoate (PHA) as components. The shear induced crystallization allowed crystallization of PHA nanofibers immediately after applying high shear rate and elongation strain, avoiding subsequent cooling to initiate crystallization. Shearing of PHA increased non-isothermal crystallization temperature by 50 °C and decreased the temperature range in which the transition from a molten state to a crystallized one occurs by 17 °C. SEM observations demonstrate the successful transformation of the dispersed PHA phase into nanofibrils with diameters of nearly 200 nm. The transition from the droplets of PHA to fibers causes the brittle-to-ductile transition of the PLA matrix at a low concentration of PHA and contributes to the simultaneous increase of its rigidity and strength.