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Does amyloid fibril nucleation occur at surfaces only?

Pallbo, Jon LU orcid ; Linse, Sara LU and Olsson, Ulf LU orcid (2025) In Biophysical Journal
Abstract

The Aβ42 peptide (APP(672–713)), associated with Alzheimer disease, is highly prone to form amyloid fibrils and has been extensively studied through in vitro experiments. Such experiments represent a basis for understanding the biophysical chemistry of amyloid-related diseases. In this communication, we show that homogeneous primary nucleation in vitro of Aβ42 fibrils is a very rare event, implying that primary nucleation occurs almost exclusively at interfaces, by heterogeneous nucleation. Recognizing that the protein molecules in amyloid fibrils possess a two-dimensional fold, we discuss the nucleation in relation to protein folding and Levinthal's paradox. In the much more rapid heterogeneous nucleation, we suggest that one... (More)

The Aβ42 peptide (APP(672–713)), associated with Alzheimer disease, is highly prone to form amyloid fibrils and has been extensively studied through in vitro experiments. Such experiments represent a basis for understanding the biophysical chemistry of amyloid-related diseases. In this communication, we show that homogeneous primary nucleation in vitro of Aβ42 fibrils is a very rare event, implying that primary nucleation occurs almost exclusively at interfaces, by heterogeneous nucleation. Recognizing that the protein molecules in amyloid fibrils possess a two-dimensional fold, we discuss the nucleation in relation to protein folding and Levinthal's paradox. In the much more rapid heterogeneous nucleation, we suggest that one catalyzing effect is the significant reduction of the effective conformational space when a monomer polypeptide chain (strongly) adsorbs to a surface, facilitating its search for the target fold.

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organization
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type
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publication status
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Biophysical Journal
publisher
Cell Press
external identifiers
  • pmid:41204665
  • scopus:105022281341
ISSN
0006-3495
DOI
10.1016/j.bpj.2025.11.002
language
English
LU publication?
yes
id
f8c2a6f1-49f8-4ea2-b412-6f9a0f3967a3
date added to LUP
2026-02-09 14:43:15
date last changed
2026-05-19 04:57:20
@article{f8c2a6f1-49f8-4ea2-b412-6f9a0f3967a3,
  abstract     = {{<p>The Aβ42 peptide (APP(672–713)), associated with Alzheimer disease, is highly prone to form amyloid fibrils and has been extensively studied through in vitro experiments. Such experiments represent a basis for understanding the biophysical chemistry of amyloid-related diseases. In this communication, we show that homogeneous primary nucleation in vitro of Aβ42 fibrils is a very rare event, implying that primary nucleation occurs almost exclusively at interfaces, by heterogeneous nucleation. Recognizing that the protein molecules in amyloid fibrils possess a two-dimensional fold, we discuss the nucleation in relation to protein folding and Levinthal's paradox. In the much more rapid heterogeneous nucleation, we suggest that one catalyzing effect is the significant reduction of the effective conformational space when a monomer polypeptide chain (strongly) adsorbs to a surface, facilitating its search for the target fold.</p>}},
  author       = {{Pallbo, Jon and Linse, Sara and Olsson, Ulf}},
  issn         = {{0006-3495}},
  language     = {{eng}},
  publisher    = {{Cell Press}},
  series       = {{Biophysical Journal}},
  title        = {{Does amyloid fibril nucleation occur at surfaces only?}},
  url          = {{http://dx.doi.org/10.1016/j.bpj.2025.11.002}},
  doi          = {{10.1016/j.bpj.2025.11.002}},
  year         = {{2025}},
}