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Correlative infrared nanospectroscopy and transmission electron microscopy to investigate nanometric amyloid fibrils: prospects and challenges
摘要： Propagation of structural information through conformational changes in host-encoded amyloid proteins is at the root of many neurodegenerative disorders. Although important breakthroughs have been made in the field, fundamental issues like the 3D-structures of the fibrils involved in some of those disorders are still to be elucidated. To better characterise those nanometric fibrils, a broad range of techniques is currently available. Nevertheless none of them is able to perform direct chemical characterisation of single protein fibrils. In this work, we propose to investigate the structure of the C-terminal region of a bacterial protein called Hfq as a model amyloidogenic protein, using a correlative approach. The complementary techniques used are transmission electron microscopy and a newly developed infrared nanospectroscopy technique called AFM-IR. We introduce and discuss the strategy that we have implemented as well as the protocol, challenges and difficulties encountered during this study to characterise amyloid assemblies at the nearly single-molecule level.
关键词： correlative measurements,transmission electron microscopy,infrared nanospectroscopy,fibrils,Hfq,atomic force microscopy,Amyloid
更新于2025-09-23 15:22:29
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Non-fullerene acceptor fibrils enable efficient ternary organic solar cells with 16.6% efficiency
摘要： Optimizing the components and morphology within the photoactive layer of organic solar cells (OSCs) can significantly enhance their power conversion efficiency (PCE). A new A-D-A type non-fullerene acceptor IDMIC-4F is designed and synthesized in this work, and is employed as the third component to prepare high performance ternary solar cells. IDMIC-4F can form fibrils after solution casting, and the presence of this fibrillar structure in the PBDB-T-2F:BTP-4F host confines the growth of donors and acceptors into fine domains, as well as acting as transport channels to enhance electron mobility. Single junction ternary devices incorporating 10 wt% IDMIC-4F exhibit enhanced light absorption and balanced carrier mobility, and achieve a maximum PCE of 16.6% compared to 15.7% for the binary device, which is a remarkable efficiency for OSCs reported in literature. This non-fullerene acceptor fibril network strategy is a promising method to improve the photovoltaic performance of ternary OSCs.
关键词： ternary solar cells,non-fullerene acceptor fibrils,power conversion efficiency
更新于2025-09-19 17:13:59
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Hyperthermia Induced by Near-Infrared Laser-Irradiated CsWO3 Nanoparticles Disintegrates Preformed Lysozyme Amyloid Fibrils
摘要： This research study attempts to prove the concept of the applicability of hyperthermia to treating the lysozyme amyloid fibrils (LAF)’s self-assembled fibrillary aggregates by a feedback-modulated temperature controller ranging from 26 °C to 80 °C, and separately, by near-infrared (NIR) laser-irradiated cesium tungstate (CsWO3) nanoparticle (NPs). The dependence of the final morphology of the amyloidal assembly on external heating and the photothermal effect of the NPs on treating the fibrillary assembly were investigated and analyzed. Experimentally, atomic force microscopy (AFM), optical stereoscopy, and scanning electron microscopy (SEM) were used primarily to ensure mutual interaction between LAF and NPs, optically elucidate the surface contour and final fibrillary assembly upon the influence of thermal treatment, and further reveal fine-details of the optical samples. Finally, conclusive remarks are drawn that the fibrillary structures doped with the NPs exhibit an increasing degree of unique orthogonality. As the temperature rises, utter deformation of the dendritic structures of fibrillary assemblies at 70 °C was found, and NIR laser-irradiated CsWO3 NPs have been demonstrated to be useful in topically destructing pre-assembled LAFs, which may be conducive to the future development of neurodegenerative therapeutic techniques.
关键词： neurodegenerative diseases,self-assembled nanocomposite,lysozyme amyloid fibrils,hyperthermia,cesium tungsten oxide nanoparticles
更新于2025-09-16 10:30:52
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Changing Times: Fluorescence-Lifetime Analysis of Amyloidogenic SF-IAPP Fusion Protein
摘要： In a number of conformational diseases, intracellular accumulation of proteins bearing non-native conformations occurs. The search for compounds that are capable of hindering the formation and accumulation of toxic protein aggregates and fibrils is an urgent task. Present fluorescent methods of fibrils’ detection prevent simple real-time observations. We suppose to use green fluorescent protein fused with target protein and fluorescence lifetime measurement technique for this purpose. The recombinant proteins analyzed were produced in E. coli. Mass spectrometry was used for the primary structure of the recombinant proteins and post-translational modifications identification. The fluorescence lifetime of the superfolder green fluorescent protein (SF) and the SF protein fused with islet amyloid polypeptide (SF-IAPP) were studied in polyacrylamide gel using Fluorescent-Lifetime Imaging Microscopy (FLIM). It was shown that the SF average fluorescence lifetime in gel slightly differs from that of the SF-IAPP monomer under these conditions. SF-IAPP does not lose the ability to form amyloid-like fibrils. Under the same conditions (in polyacrylamide gel), SF and SF-IAPP monomers have similar fluorescence time characteristics and the average fluorescence lifetime of SF-IAPP in fibrils significantly decreases. We propose the application of FLIM to the measurement of average fluorescence lifetimes of fusion proteins (amyloidogenic protein-SF) in the context of studies using cellular models of conformational diseases.
关键词： FLIM,IAPP,amyloid-like fibrils,green fluorescent protein,atomic force microscopy,conformational diseases
更新于2025-09-09 09:28:46
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Rational structure‐based design of fluorescence probes for amyloid folds
摘要： Amyloid fibrils are pathological hallmark of various human diseases - including Parkinson’s Alzheimer’s, ALS, Prion diseases. Treatment of the amyloid diseases are hindered amongst other factors also due to timely detection and therefore, early detection of the amyloid fibrils would be beneficial for the treatment against these disorders. Here, we report a small molecular fluorescent probe that selectively recognize the fibrillar form of Amyloid beta(1-42), a-Synuclein, and HET-s(218-289) protein over their monomeric conformation. The rational design of the reporters relies on the well-known cross-b-sheet repetition motif, the key structural feature of amyloids.
关键词： HET-s,fluorescence probes,amyloid fibrils,a-Syn,Ab(1-42)
更新于2025-09-04 15:30:14