Jiangtao Zhou

Last Name

Zhou

First Name

Jiangtao

ORCID

0000-0003-4248-2207

Show all metadata

Search Results

Publications1 - 10 of 40

Cell invasive amyloid assemblies from SARS-CoV-2 peptides can form multiple polymorphs with varying neurotoxicity
Sanislav, Oana; Tetaj, Rina; Metali; et al. (2024)
Nanoscale
The neurological symptoms of COVID-19, often referred to as neuro-COVID include neurological pain, memory loss, cognitive and sensory disruption. These neurological symptoms can persist for months and are known as Post-Acute Sequalae of COVID-19 (PASC). The molecular origins of neuro-COVID, and how it contributes to PASC are unknown, however a growing body of research highlights that the self-assembly of protein fragments from SARS-CoV-2 into amyloid nanofibrils may play a causative role. Previously, we identified two fragments from the SARS-CoV-2 proteins, Open Reading Frame (ORF) 6 and ORF10, that self-assemble into neurotoxic amyloid assemblies. Here we further our understanding of the self-assembly mechanisms and nano-architectures formed by these fragments and their biological responses. By solubilising the peptides in a fluorinated solvent, we eliminate insoluble aggregates in the starting materials (seeds) that change the polymorphic landscape of the assemblies. The resultant assemblies are dominated by structures with higher free energies (e.g. ribbons and amorphous aggregates) that are less toxic to cultured neurons but do affect their mitochondrial respiration. We also show the first direct evidence of cellular uptake of viral amyloids. This work highlights the importance of understanding the polymorphic behaviour of amyloids and the correlation to neurotoxicity, particularly in the context of neuro-COVID and PASC.
Hierarchical Protofilament Intertwining Rules the Formation of Mixed-Curvature Amyloid Polymorphs
Zhou, Jiangtao; Assenza, Salvatore; Tatli, Meltem; et al. (2024)
Advanced Science
Amyloid polymorphism is a hallmark of almost all amyloid species, yet the mechanisms underlying the formation of amyloid polymorphs and their complex architectures remain elusive. Commonly, two main mesoscopic topologies are found in amyloid polymorphs characterized by non-zero Gaussian and mean curvatures: twisted ribbons and helical fibrils, respectively. Here, a rich heterogeneity of configurations is demonstrated on insulin amyloid fibrils, where protofilament packing can occur, besides the common polymorphs, also in a combined mode forming mixed-curvature polymorphs. Through AFM statistical analysis, an extended array of heterogeneous architectures that are rationalized by mesoscopic theoretical arguments are identified. Notably, an unusual fibrillization pathway is also unraveled toward mixed-curvature polymorphs via the widespread recruitment and intertwining of protofilaments and protofibrils. The results present an original view of amyloid polymorphism and advance the fundamental understanding of the fibrillization mechanism from single protofilaments into mature amyloid fibrils.
Protease-Mediated Synthesis of Zein Nanofibrils: From Structural Elucidation to Functional Application
Li, Mingqin; Jin, Tonghui; Wüthrich, Simone; et al. (2025)
Advanced Science
The fibrillization of plant-based proteins enhances their functionality, enabling potential applications in food and sustainable materials. Zein, a highly hydrophobic protein from corn, is a versatile industrial ingredient, but its functionality is limited to environments containing high levels of organic solvents. This study aims to develop a protease-assisted approach for synthesizing zein nanofibrils as functional building blocks, eliminating the need for organic solvents in the conventional process. Through proteomics, microscopy, and spectroscopy, the bioprocess and structural features of these novel nanofibrils are characterized. The results reveal that over 50% of α-zein sequence is prone to fibrillization, with pepsin demonstrating a clear advantage in efficiently releasing fibrillization-prone peptide segments (bioconversion > 70%) and producing a peptide mixture suitable for self-assembly. The fibrillization process is significantly enhanced by increasing peptide concentration and adding the anionic surfactant sodium dodecyl sulfate, which can lead to the formation of semiflexible fibrils with amyloid-like β-sheet structures. These nanofibrils outperformed native zein as emulsifiers in high internal phase emulsions and are able to form fibrous hydrogels. The protease-assisted fibrillization process achieved in this study provides an effective solution for expanding applications of zein or corn proteins in a purely aqueous environment.
Photo-reversible amyloid nanoNETs for regenerative antimicrobial therapies
Xuan, Qize; Li, Hui; Gao, Yuan; et al. (2025)
Nature Communications
Drug-resistant bacterial infections, exacerbated by antibiotic resistance and biofilm resilience, disrupt tissue repair through dysregulated inflammation and impaired regeneration. Neutrophil extracellular traps (NETs) play a crucial role in endogenous immunity by entrapping and eliminating pathogens, inspiring the development of synthetic biomaterials that replicate this function. However, current synthetic NETs face challenges in complexity, biocompatibility, structural integrity and effectiveness. Here, we present a NETs-mimicking hydrogel composed of reversible lysozyme amyloid flexible nanofibrils (FFs) enabling pathogen elimination and tissue regeneration. The FFs therein self-assemble from natural egg-white lysozyme endowing these nanoNETs with bioactivity against pathogens, and when duly labeled to respond to near-infrared irradiation, they disassemble into unfolded lysozyme monomers with antimicrobial activity. Notably, the hydrogel disassembly is followed by the controlled release of pre-dissolved Mg²⁺ ions, reprogramming macrophages toward a pro-regenerative phenotype and mitigating inflammation. In both murine and porcine models, these biocompatible nanoNETs demonstrate excellent antibacterial performance, accelerating healing of wounds infected by methicillin-resistant Staphylococcus aureus (MRSA). Moreover, these nanoNETs boost in-vivo healing of MRSA-infected periprosthetic joints, preserving osteogenic and regenerative microenvironments. These results build on the reversible nature of flexible amyloids to introduce stimuli-responsive biocompatible nanoNETs with significant potential for antimicrobial and regenerative therapies in bacterial-resistant infections.
Formation and characterization of plant-based amyloid fibrils from hemp seed protein
Kutzli, Ines; Zhou, Jiangtao; Li, Ting; et al. (2023)
Food Hydrocolloids
Amyloid fibrils from plant-based food protein sources bear a large unexploited potential for applications in food and other biomaterials due to their techno-functional features. However, their low solubility and highly complex, inhomogeneous protein composition often hamper fibrillization. The objective of this study was to evaluate the feasibility of amyloid fibril production from hemp seed protein, known as a sustainable and low-allergenic protein source. Hemp protein concentrate (HPC), primarily constituted of the 11 S globulin edestin, with 89.0% protein solubility (0.25% w/w HPC, pH 2) was extracted using gentle micellization. Fibrillization of HPC (2% w/w, pH 2, 90 °C, 300 rpm) was monitored over 5 h by ThT fluorescence, exhibiting a steep increase in fluorescence signal after a lag phase of 180 min. SDS-PAGE analysis indicated progressive polypeptide hydrolysis upon heating and the formation of large proteinaceous aggregates after 160 min. Conformational changes towards increased β-sheet content were demonstrated by CD and FTIR. The morphology of the formed fibrillar aggregates was characterized by TEM and AFM. While essentially linear, branching effects of the fibrils became visible and kept increasing with incubation time. After a relatively short incubation time of 4 h, fibrils had an average height of 7.8 nm, a contour length of 1.8 μm, and a persistence length of ∼2.7 μm. These results suggest, that under the chosen conditions for protein extraction and incubation, HPC forms relatively flexible amyloid fibrils with a high aspect ratio and tendency to form branches. By revealing the potential of hemp seed proteins for amyloid fibril formation, these results contribute to expand the understanding of plant protein fibrillization.
Toxin-Responsive Antigen Reservoir Nanovaccines for In Situ Vaccination Against Bacterial Infection Recurrence
Xuan, Qize; Jiang, Feng; Qiao, Xinchi; et al. (2025)
Advanced Functional Materials
Current bacterial vaccines remain unsatisfactory in combating the increasing recurrence rates of drug-resistant bacterial infections due to the inefficient activation of antigen presenting cells and the absence of long-term immune memory. Here, a therapeutic nanovaccine (RBCM@PPPB) is engineered based on a photoimmunotherapy strategy and fabricated using polydopamine (PDA)-modified Prussian blue nanoparticles, coated with targeting peptides and red blood cell membrane. These features enhance their biosafety and responsiveness to toxins from methicillin-resistant Staphylococcus aureus (MRSA). The targeting peptides guide the nanoparticles to infection sites, allowing them to accumulate on the MRSA surface. Under near-infrared irradiation, the photothermal bactericidal effect triggers the antigens release from dead MRSA, creating a diverse bacterial antigen library. PDA coating endows the nanoparticles with robust bacterial antigen-gathering capacity, enabling in situ vaccination that enhances the antigen presentation process and subsequent MRSA-specific adaptive immunity. Re-challenge experiments demonstrated that RBCM@PPPB induced both cellular and humoral immune memory, significantly reducing recurrence risks. This study offers a proof-of-concept for "antigen reservoir" nanovaccines-enhanced in situ vaccination, which establishes long-term immune memory to prevent infection recurrence.
Amyloid-polysaccharide interfacial coacervates as therapeutic materials
Peydayesh, Mohammad; Kistler, Sabrina; Zhou, Jiangtao; et al. (2023)
Nature Communications
Coacervation via liquid-liquid phase separation provides an excellent opportunity to address the challenges of designing nanostructured biomaterials with multiple functionalities. Protein-polysaccharide coacervates, in particular, offer an appealing strategy to target biomaterial scaffolds, but these systems suffer from the low mechanical and chemical stabilities of protein-based condensates. Here we overcome these limitations by transforming native proteins into amyloid fibrils and demonstrate that the coacervation of cationic protein amyloids and anionic linear polysaccharides results in the interfacial self-assembly of biomaterials with precise control of their structure and properties. The coacervates present a highly ordered asymmetric architecture with amyloid fibrils on one side and the polysaccharide on the other. We demonstrate the excellent performance of these coacervates for gastric ulcer protection by validating via an in vivo assay their therapeutic effect as engineered microparticles. These results point at amyloid-polysaccharides coacervates as an original and effective biomaterial for multiple uses in internal medicine.
Amyloid-based carbon aerogels for water purification
Peydayesh, Mohammad; Vogt, Julia; Chen, Xiulin; et al. (2022)
Chemical Engineering Journal
Water scarcity is a worldwide concern with various implications, such as widespread pollution with heavy metals and organic pollutants, resulting in global threats to the environment and human health, and calling for innovative remediation strategies. We show here that the capability of protein-based carbon aerogels for removing contaminants from water can be greatly improved by transforming proteins into amyloids before their hydrothermal carbonization. Amyloid fibrils were prepared from whey protein isolate, a by-product of the dairy industry, and upon addition to different carbohydrates, the ensued mixtures were used for carbon aerogels production. Furthermore, the generality of the approach for producing carbon aerogels was demonstrated using vegetable amyloids from soy protein. The carbon aerogels are able to adsorb Au(III), Pt(II), Fe(III), and Ag(I) with excellent removal efficiencies. Moreover, the amyloid whey lactose carbon aerogel has an adsorption capacity of 650.08 mg/g for Au(III), significantly higher than that of a carbon aerogel derived from monomer whey lactose. The reusability of the carbon aerogel is also proven over three continuous adsorption/regeneration cycles, with a stable performance in terms of removal efficiency indicating good long-term use. Taken together, the results demonstrate amyloid carbon aerogels’ capability as an efficient, sustainable, and inexpensive solution for water purification.
Photonics of Hydrothermally Treated β-Lactoglobulin Amyloids
Hanczyc, Piotr; Alfarano, Serena Rosa; Bolisetty, Sreenath; et al. (2024)
Small Science
Increased temperature and high pressure are applied to beta-lactoglobulin fibrils in the autoclave, resulting in the acquisition of a composite material comprised of partially disassembled amyloid fibrils and carbon dots. Confirmation of the preservation of the beta-sheet motif attributed to amyloids in the hydrothermally treated fibrils is obtained through wide-angle X-ray scattering and ThT assay. Z-scan analysis reveals a two-photon absorption (2PA) enhancement in the low-lying transition band (Lₐ) of tyrosine, while quantum chemical calculations demonstrate a correlation between the yield of 2PA and the interspace distance between aromatic residues. Overall, the intrinsic optical properties of amyloid fibrils treated in a subcritical water environment are found to be linked with the π-conjugation of tyrosine units and their through-space coupling. The resulting composite material is employed as a coating for a commercial ultraviolet light-emitting diode lamp, showcasing the potential utility of sustainable biomaterials with improved optical properties for photonics applications.
An evolutionarily conserved mechanism controls reversible amyloids of pyruvate kinase via pH-sensing regions
Cereghetti, Gea; Kissling, Vera M.; Koch, Lisa M.; et al. (2024)
Developmental Cell
Amyloids are known as irreversible aggregates associated with neurodegenerative diseases. However, recent evidence shows that a subset of amyloids can form reversibly and fulfill essential cellular functions. Yet, the molecular mechanisms regulating functional amyloids and distinguishing them from pathological aggregates remain unclear. Here, we investigate the conserved principles of amyloid reversibility by studying the essential metabolic enzyme pyruvate kinase (PK) in yeast and human cells. We demonstrate that yeast PK (Cdc19) and human PK (PKM2) form reversible amyloids through a pH-sensitive amyloid core. Stress-induced cytosolic acidification promotes aggregation via protonation of specific glutamate (yeast) or histidine (human) residues within the amyloid core. Mutations mimicking protonation cause constitutive PK aggregation, while non-protonatable PK mutants remain soluble even upon stress. Physiological PK aggregation is coupled to metabolic rewiring and glycolysis arrest, causing severe growth defects when misregulated. Our work thus identifies an evolutionarily conserved, potentially widespread mechanism regulating functional amyloids during stress.

Publications1 - 10 of 40

Jiangtao Zhou

Last Name

First Name

ORCID

Organisational unit

Filters

Search Results