High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways
Individual Alzheimer’s disease (AD) patients have been shown to have structurally distinct amyloid-β (Aβ) aggregates, including fibrils, in their brain. These findings suggest the possibility of a relationship between AD progression and Aβ fibril structures. Thus, the characterization of the structu...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/12/4287 |
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| author | Takahiro Watanabe-Nakayama Bikash R. Sahoo Ayyalusamy Ramamoorthy Kenjiro Ono |
| author_facet | Takahiro Watanabe-Nakayama Bikash R. Sahoo Ayyalusamy Ramamoorthy Kenjiro Ono |
| author_sort | Takahiro Watanabe-Nakayama |
| collection | DOAJ |
| description | Individual Alzheimer’s disease (AD) patients have been shown to have structurally distinct amyloid-β (Aβ) aggregates, including fibrils, in their brain. These findings suggest the possibility of a relationship between AD progression and Aβ fibril structures. Thus, the characterization of the structural dynamics of Aβ could aid the development of novel therapeutic strategies and diagnosis. Protein structure and dynamics have typically been studied separately. Most of the commonly used biophysical approaches are limited in providing substantial details regarding the combination of both structure and dynamics. On the other hand, high-speed atomic force microscopy (HS-AFM), which simultaneously visualizes an individual protein structure and its dynamics in liquid in real time, can uniquely link the structure and the kinetic details, and it can also unveil novel insights. Although amyloidogenic proteins generate heterogeneously aggregated species, including transient unstable states during the aggregation process, HS-AFM elucidated the structural dynamics of individual aggregates in real time in liquid without purification and isolation. Here, we review and discuss the HS-AFM imaging of amyloid aggregation and strategies to optimize the experiments showing findings from Aβ and amylin, which is associated with type II diabetes, shares some common biological features with Aβ, and is reported to be involved in AD. |
| first_indexed | 2024-03-10T19:08:40Z |
| format | Article |
| id | doaj.art-de20953a28f94243b27b02c6c5b8a058 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:08:40Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-de20953a28f94243b27b02c6c5b8a0582023-11-20T04:01:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012112428710.3390/ijms21124287High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation PathwaysTakahiro Watanabe-Nakayama0Bikash R. Sahoo1Ayyalusamy Ramamoorthy2Kenjiro Ono3WPI Nano Life Science Institute, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, JapanBiophysics Program, Department of Chemistry, Macromolecular Science and Engineering, and Biomedical Engineering, The University of Michigan, Ann Arbor, MI 48109-1055, USABiophysics and Department of Chemistry, University of Michigan, Ann Arbor, MI 48109-1055, USADivision of Neurology, Department of Internal Medicine, School of Medicine, Showa University, Hatanodai, Shinagawa district, Tokyo 142-8666, JapanIndividual Alzheimer’s disease (AD) patients have been shown to have structurally distinct amyloid-β (Aβ) aggregates, including fibrils, in their brain. These findings suggest the possibility of a relationship between AD progression and Aβ fibril structures. Thus, the characterization of the structural dynamics of Aβ could aid the development of novel therapeutic strategies and diagnosis. Protein structure and dynamics have typically been studied separately. Most of the commonly used biophysical approaches are limited in providing substantial details regarding the combination of both structure and dynamics. On the other hand, high-speed atomic force microscopy (HS-AFM), which simultaneously visualizes an individual protein structure and its dynamics in liquid in real time, can uniquely link the structure and the kinetic details, and it can also unveil novel insights. Although amyloidogenic proteins generate heterogeneously aggregated species, including transient unstable states during the aggregation process, HS-AFM elucidated the structural dynamics of individual aggregates in real time in liquid without purification and isolation. Here, we review and discuss the HS-AFM imaging of amyloid aggregation and strategies to optimize the experiments showing findings from Aβ and amylin, which is associated with type II diabetes, shares some common biological features with Aβ, and is reported to be involved in AD.https://www.mdpi.com/1422-0067/21/12/4287molecular imagingamyloid β-peptidesislet amyloid polypeptidehigh-speed atomic force microscopy |
| spellingShingle | Takahiro Watanabe-Nakayama Bikash R. Sahoo Ayyalusamy Ramamoorthy Kenjiro Ono High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways International Journal of Molecular Sciences molecular imaging amyloid β-peptides islet amyloid polypeptide high-speed atomic force microscopy |
| title | High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways |
| title_full | High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways |
| title_fullStr | High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways |
| title_full_unstemmed | High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways |
| title_short | High-Speed Atomic Force Microscopy Reveals the Structural Dynamics of the Amyloid-β and Amylin Aggregation Pathways |
| title_sort | high speed atomic force microscopy reveals the structural dynamics of the amyloid β and amylin aggregation pathways |
| topic | molecular imaging amyloid β-peptides islet amyloid polypeptide high-speed atomic force microscopy |
| url | https://www.mdpi.com/1422-0067/21/12/4287 |
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