scholarly journals Different Aggregation Pathways and Structures for Aβ40 and Aβ42 Peptides

Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 198
Author(s):  
Li Wang ◽  
Kilho Eom ◽  
Taeyun Kwon
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Β ◽  
Vital Role ◽  
Aggregation Process ◽  
Aβ Peptides ◽  
Force Microscopy ◽  
Atomic Force ◽  
Different Shapes ◽  
In The Beginning ◽  
Self Aggregation

Self-aggregation of amyloid-β (Aβ) peptides has been known to play a vital role in the onset stage of neurodegenerative diseases, indicating the necessity of understanding the aggregation process of Aβ peptides. Despite previous studies on the aggregation process of Aβ peptides, the aggregation pathways of Aβ isoforms (i.e., Aβ40 and Aβ42) and their related structures have not been fully understood yet. Here, we study the aggregation pathways of Aβ40 and Aβ42, and the structures of Aβ40 and Aβ42 aggregates during the process, based on fluorescence and atomic force microscopy (AFM) experiments. It is shown that in the beginning of aggregation process for both Aβ40 and Aβ42, a number of particles (i.e., spherical oligomers) are formed. These particles are subsequently self-assembled together, resulting in the formation of different shapes of amyloid fibrils. Our finding suggests that the different aggregation pathways of Aβ isoforms lead to the amyloid fibrils with contrasting structure.

scholarly journals Cytotoxic Aβ Protofilaments Are Generated in the Process of Aβ Fibril Disaggregation

2021 ◽  
Vol 22 (23) ◽  
pp. 12780
Author(s):  
Toshisuke Kaku ◽  
Kaori Tsukakoshi ◽  
Kazunori Ikebukuro
Keyword(s):  
Amyloid Fibrils ◽  
Epigallocatechin Gallate ◽  
Amyloid Β ◽  
Neural Cells ◽  
Aβ Oligomers ◽  
Microscopy Imaging ◽  
Force Microscopy ◽  
Atomic Force ◽  
Significant Research ◽  
Aβ Fibrils

Significant research on Alzheimer’s disease (AD) has demonstrated that amyloid β (Aβ) oligomers are toxic molecules against neural cells. Thus, determining the generation mechanism of toxic Aβ oligomers is crucial for understanding AD pathogenesis. Aβ fibrils were reported to be disaggregated by treatment with small compounds, such as epigallocatechin gallate (EGCG) and dopamine (DA), and a loss of fibril shape and decrease in cytotoxicity were observed. However, the characteristics of intermediate products during the fibril disaggregation process are poorly understood. In this study, we found that cytotoxic Aβ aggregates are generated during a moderate disaggregation process of Aβ fibrils. A cytotoxicity assay revealed that Aβ fibrils incubated with a low concentration of EGCG and DA showed higher cytotoxicity than Aβ fibrils alone. Atomic force microscopy imaging and circular dichroism spectrometry showed that short and narrow protofilaments, which were highly stable in the β-sheet structure, were abundant in these moderately disaggregated samples. These results indicate that toxic Aβ protofilaments are generated during disaggregation from amyloid fibrils, suggesting that disaggregation of Aβ fibrils by small compounds may be one of the possible mechanisms for the generation of toxic Aβ aggregates in the brain.

scholarly journals Dual Size-Dependent Effect of Fe3O4 Magnetic Nanoparticles Upon Interaction with Lysozyme Amyloid Fibrils: Disintegration and Adsorption

Nanomaterials ◽  
2018 ◽  
Vol 9 (1) ◽  
pp. 37 ◽  
Author(s):  
Natália Tomašovičová ◽  
Po-Sheng Hu ◽  
Cyun-Lun Zeng ◽  
Jozefína Majorošová ◽  
Katarína Zakutanská ◽  
...  
Keyword(s):  
Magnetic Nanoparticles ◽  
Amyloid Fibrils ◽  
Volume Concentration ◽  
Amyloid Β ◽  
Fe3o4 Magnetic Nanoparticles ◽  
Force Microscopy ◽  
Size Dependent ◽  
Egg White Lysozyme ◽  
Atomic Force ◽  
20 Nm

Nanomedicine compounds containing nanoparticles, such as iron oxides and gold, have been demonstrated to be effective in promoting different magnitudes of interaction with amyloid β fibrils, of which disintegrating or inhibiting effects are of great importance to treating fibrillary aggregation-induced neurological disorders such as Alzheimer’s disease. This research herein studies the interaction between lysozyme amyloid fibrils, a type of fibers derived from hen egg white lysozyme, and Fe3O4 magnetic nanoparticles (MNPs) of an assorted diameter sizes of 5 nm, 10 nm and 20 nm, using atomic force microscopy (AFM). Specifically, the effects of the sizes of negatively charged MNPs on the resultant amyloid fibrillary mixture was investigated. Our results of AFM images indicated that the interaction between MNPs and the fibrils commences immediately after adding MNPs to the fibril solution, and the actions of such MNPs-doped fibrillary interplay, either integration or segmentation, is strongly dependent on the size and volume concentration of MNPs. In the cases of 5 nm and 20 nm particles of equivalent volume concentration, the adsorption and agglomeration of MNPs onto the fibrillary surfaces was observed, whereas, interestingly, MNPs with diameter size of 10 nm enables segmentation of the slender fibrils into debris when a proper implemented volume concentration was found, which signifies utter destruction of the amyloid fibrillary structure.

scholarly journals Valorization of Apple Peels through the Study of the Effects on the Amyloid Aggregation Process of κ-Casein

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2371
Author(s):  
Valeria Guarrasi ◽  
Giacoma Cinzia Rappa ◽  
Maria Assunta Costa ◽  
Fabio Librizzi ◽  
Marco Raimondo ◽  
...  
Keyword(s):  
Protein Aggregation ◽  
Environmental Sustainability ◽  
Bovine Milk ◽  
Amyloid Formation ◽  
Aggregation Process ◽  
Amyloid Aggregation ◽  
Social Challenges ◽  
Force Microscopy ◽  
Atomic Force ◽  
Apple Peels

Waste valorization represents one of the main social challenges when promoting a circular economy and environmental sustainability. Here, we evaluated the effect of the polyphenols extracted from apple peels, normally disposed of as waste, on the amyloid aggregation process of κ-casein from bovine milk, a well-used amyloidogenic model system. The effect of the apple peel extract on protein aggregation was examined using a thioflavin T fluorescence assay, Congo red binding assay, circular dichroism, light scattering, and atomic force microscopy. We found that the phenolic extract from the peel of apples of the cultivar “Fuji”, cultivated in Sicily (Caltavuturo, Italy), inhibited κ-casein fibril formation in a dose-dependent way. In particular, we found that the extract significantly reduced the protein aggregation rate and inhibited the secondary structure reorganization that accompanies κ-casein amyloid formation. Protein-aggregated species resulting from the incubation of κ-casein in the presence of polyphenols under amyloid aggregation conditions were reduced in number and different in morphology.

scholarly journals Evaluation of grain boundaries as percolation pathways in quartz-rich continental crust using Atomic Force Microscopy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ritabrata Dobe ◽  
Anuja Das ◽  
Rabibrata Mukherjee ◽  
Saibal Gupta
Keyword(s):  
Atomic Force Microscopy ◽  
Grain Boundary ◽  
Continental Crust ◽  
Electron Backscatter Diffraction ◽  
Vital Role ◽  
Force Microscopy ◽  
Atomic Force ◽  
Width Measurements ◽  
Lower Temperature ◽  
Backscatter Diffraction

AbstractHydrous fluids play a vital role in the chemical and rheological evolution of ductile, quartz-bearing continental crust, where fluid percolation pathways are controlled by grain boundary domains. In this study, widths of grain boundary domains in seven quartzite samples metamorphosed under varying crustal conditions were investigated using Atomic Force Microscopy (AFM) which allows comparatively easy, high magnification imaging and precise width measurements. It is observed that dynamic recrystallization at higher metamorphic grades is much more efficient at reducing grain boundary widths than at lower temperature conditions. The concept of force-distance spectroscopy, applied to geological samples for the first time, allows qualitative estimation of variations in the strength of grain boundary domains. The strength of grain boundary domains is inferred to be higher in the high grade quartzites, which is supported by Kernel Average Misorientation (KAM) studies using Electron Backscatter Diffraction (EBSD). The results of the study show that quartzites deformed and metamorphosed at higher grades have narrower channels without pores and an abundance of periodically arranged bridges oriented at right angles to the length of the boundary. We conclude that grain boundary domains in quartz-rich rocks are more resistant to fluid percolation in the granulite rather than the greenschist facies.

scholarly journals Probing the Influence of Single-Site Mutations in the Central Cross-β Region of Amyloid β (1–40) Peptides

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1848
Author(s):  
Jacob Fritzsch ◽  
Alexander Korn ◽  
Dayana Surendran ◽  
Martin Krueger ◽  
Holger A. Scheidt ◽  
...  
Keyword(s):  
Amyloid Fibrils ◽  
Amyloid Β ◽  
Neuronal Cell ◽  
Cell Toxicity ◽  
X Ray Diffraction ◽  
Hydrophobic Contact ◽  
Aβ Peptides ◽  
Tht Fluorescence ◽  
Modified Peptides ◽  
Aβ Fibrils

Amyloid β (Aβ) is a peptide known to form amyloid fibrils in the brain of patients suffering from Alzheimer’s disease. A complete mechanistic understanding how Aβ peptides form neurotoxic assemblies and how they kill neurons has not yet been achieved. Previous analysis of various Aβ40 mutants could reveal the significant importance of the hydrophobic contact between the residues Phe19 and Leu34 for cell toxicity. For some mutations at Phe19, toxicity was completely abolished. In the current study, we assessed if perturbations introduced by mutations in the direct proximity of the Phe19/Leu34 contact would have similar relevance for the fibrillation kinetics, structure, dynamics and toxicity of the Aβ assemblies. To this end, we rationally modified positions Phe20 or Gly33. A small library of Aβ40 peptides with Phe20 mutated to Lys, Tyr or the non-proteinogenic cyclohexylalanine (Cha) or Gly33 mutated to Ala was synthesized. We used electron microscopy, circular dichroism, X-ray diffraction, solid-state NMR spectroscopy, ThT fluorescence and MTT cell toxicity assays to comprehensively investigate the physicochemical properties of the Aβ fibrils formed by the modified peptides as well as toxicity to a neuronal cell line. Single mutations of either Phe20 or Gly33 led to relatively drastic alterations in the Aβ fibrillation kinetics but left the global, as well as the local structure, of the fibrils largely unchanged. Furthermore, the introduced perturbations caused a severe decrease or loss of cell toxicity compared to wildtype Aβ40. We suggest that perturbations at position Phe20 and Gly33 affect the fibrillation pathway of Aβ40 and, thereby, influence the especially toxic oligomeric species manifesting so that the region around the Phe19/Leu34 hydrophobic contact provides a promising site for the design of small molecules interfering with the Aβ fibrillation pathway.

scholarly journals Planar Boronic Graphene and Nitrogenized Graphene Heterostructure for Protein Stretch and Confinement

Biomolecules ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 1756
Author(s):  
Xuchang Su ◽  
Zhi He ◽  
Lijun Meng ◽  
Hong Liang ◽  
Ruhong Zhou
Keyword(s):  
Single Molecule ◽  
Intrinsically Disordered Proteins ◽  
Electron Tunneling ◽  
Amyloid Β ◽  
Protein Sequencing ◽  
Disordered Proteins ◽  
Force Microscopy ◽  
Intrinsically Disordered ◽  
Atomic Force ◽  
Dynamics Simulations

Single-molecule techniques such as electron tunneling and atomic force microscopy have attracted growing interests in protein sequencing. For these methods, it is critical to refine and stabilize the protein sample to a “suitable mode” before applying a high-fidelity measurement. Here, we show that a planar heterostructure comprising boronic graphene (BC3) and nitrogenized graphene (C3N) sandwiched stripe (BC3/C3N/BC3) is capable of the effective stretching and confinement of three types of intrinsically disordered proteins (IDPs), including amyloid-β (1–42), polyglutamine (Q42), and α-Synuclein (61–95). Our molecular dynamics simulations demonstrate that the protein molecules interact more strongly with the C3N stripe than the BC3 one, which leads to their capture, elongation, and confinement along the center C3N stripe of the heterostructure. The conformational fluctuations of IDPs are substantially reduced after being stretched. This design may serve as a platform for single-molecule protein analysis with reduced thermal noise.

scholarly journals Subwavelength hole arrays with nanoapertures fabricated by scanning probe nanolithography

2006 ◽  
Vol 38 (2) ◽  
pp. 117-123 ◽  
Author(s):  
Z. Jaksic ◽  
M. Maksimovic ◽  
D. Vasiljevic-Radovic ◽  
M. Sarajlic
Keyword(s):  
Building Blocks ◽  
Scanning Probe ◽  
Positive Photoresist ◽  
Force Microscopy ◽  
Atomic Force ◽  
Optical Effects ◽  
Different Shapes ◽  
Subwavelength Hole Arrays ◽  
Hole Arrays ◽  
Electromagnetic Transmission

Owing to their surface plasmon-based operation, arrays of subwavelength holes show extraordinary electromagnetic transmission and intense field localizations of several orders of magnitude. Thus they were proposed as the basic building blocks for a number of applications utilizing the enhancement of nonlinear optical effects. We designed and simulated nanometer-sized subwavelength holes using an analytical approach. In our experiments we used the scanning probe method for nanolithographic fabrication of subwavelength hole arrays in silver layers sputtered on a positive photoresist substrate. We fabricated ordered nanohole patterns with different shapes, dispositions and proportions. The smallest width was about 60 nm. We characterized the fabricated samples by atomic force microscopy.

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