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Scavenging amyloid oligomers from neurons with silica nanobowls: Implications for amyloid diseases

Amyloid-β (Aβ) oligomers are toxic species implicated in Alzheimer’s disease (AD). The prevailing hypothesis implicates a major role of membrane-associated amyloid oligomers in AD pathology. Our silica nanobowls (NB) coated with lipid-polymer have submicromolar affinity for Aβ binding. We demonstrat...

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Detalles Bibliográficos
Autores principales: Sant, Vrinda, Som, Madhura, Karkisaval, Abhijith G., Carnahan, Parker, Lal, Ratnesh
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Biophysical Society 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391079/
https://www.ncbi.nlm.nih.gov/pubmed/34242592
http://dx.doi.org/10.1016/j.bpj.2021.07.002
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author Sant, Vrinda
Som, Madhura
Karkisaval, Abhijith G.
Carnahan, Parker
Lal, Ratnesh
author_facet Sant, Vrinda
Som, Madhura
Karkisaval, Abhijith G.
Carnahan, Parker
Lal, Ratnesh
author_sort Sant, Vrinda
collection PubMed
description Amyloid-β (Aβ) oligomers are toxic species implicated in Alzheimer’s disease (AD). The prevailing hypothesis implicates a major role of membrane-associated amyloid oligomers in AD pathology. Our silica nanobowls (NB) coated with lipid-polymer have submicromolar affinity for Aβ binding. We demonstrate that NB scavenges distinct fractions of Aβs in a time-resolved manner from amyloid precursor protein-null neuronal cells after incubation with Aβ. At short incubation times in cell culture, NB-Aβ seeds have aggregation kinetics resembling that of extracellular fraction of Aβ, whereas at longer incubation times, NB-Aβ seeds scavenge membrane-associated Aβ. Aβ aggregates can be eluted from NB surfaces by mechanical agitation and appear to retain their aggregation driving domains as seen in seeding aggregation experiments. These results demonstrate that the NB system can be used for time-resolved separation of toxic Aβ species from biological samples for characterization and in diagnostics. Scavenging membrane-associated amyloids using lipid-functionalized NB without chemical manipulation has wide applications in the diagnosis and therapy of AD and other neurodegenerative diseases, cancer, and cardiovascular conditions.
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spelling pubmed-83910792022-08-17 Scavenging amyloid oligomers from neurons with silica nanobowls: Implications for amyloid diseases Sant, Vrinda Som, Madhura Karkisaval, Abhijith G. Carnahan, Parker Lal, Ratnesh Biophys J Articles Amyloid-β (Aβ) oligomers are toxic species implicated in Alzheimer’s disease (AD). The prevailing hypothesis implicates a major role of membrane-associated amyloid oligomers in AD pathology. Our silica nanobowls (NB) coated with lipid-polymer have submicromolar affinity for Aβ binding. We demonstrate that NB scavenges distinct fractions of Aβs in a time-resolved manner from amyloid precursor protein-null neuronal cells after incubation with Aβ. At short incubation times in cell culture, NB-Aβ seeds have aggregation kinetics resembling that of extracellular fraction of Aβ, whereas at longer incubation times, NB-Aβ seeds scavenge membrane-associated Aβ. Aβ aggregates can be eluted from NB surfaces by mechanical agitation and appear to retain their aggregation driving domains as seen in seeding aggregation experiments. These results demonstrate that the NB system can be used for time-resolved separation of toxic Aβ species from biological samples for characterization and in diagnostics. Scavenging membrane-associated amyloids using lipid-functionalized NB without chemical manipulation has wide applications in the diagnosis and therapy of AD and other neurodegenerative diseases, cancer, and cardiovascular conditions. The Biophysical Society 2021-08-17 2021-07-07 /pmc/articles/PMC8391079/ /pubmed/34242592 http://dx.doi.org/10.1016/j.bpj.2021.07.002 Text en © 2021 Biophysical Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Articles
Sant, Vrinda
Som, Madhura
Karkisaval, Abhijith G.
Carnahan, Parker
Lal, Ratnesh
Scavenging amyloid oligomers from neurons with silica nanobowls: Implications for amyloid diseases
title Scavenging amyloid oligomers from neurons with silica nanobowls: Implications for amyloid diseases
title_full Scavenging amyloid oligomers from neurons with silica nanobowls: Implications for amyloid diseases
title_fullStr Scavenging amyloid oligomers from neurons with silica nanobowls: Implications for amyloid diseases
title_full_unstemmed Scavenging amyloid oligomers from neurons with silica nanobowls: Implications for amyloid diseases
title_short Scavenging amyloid oligomers from neurons with silica nanobowls: Implications for amyloid diseases
title_sort scavenging amyloid oligomers from neurons with silica nanobowls: implications for amyloid diseases
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8391079/
https://www.ncbi.nlm.nih.gov/pubmed/34242592
http://dx.doi.org/10.1016/j.bpj.2021.07.002
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