Rapid fragmentation during seeded lysozyme aggregation revealed at the single molecule level

Research output: Contribution to journalArticle

Authors

  • Marketa Kubankova
  • Xiaoyan Lin
  • Tim Albrecht
  • Joshua B Edel
  • Marina K Kuimova

Colleges, School and Institutes

Abstract

Protein aggregation is associated with neurodegenerative disorders such as Alzheimer's and Parkinson's diseases. The poorly understood pathogenic mechanism of amyloid diseases makes early stage diagnostics or therapeutic intervention a challenge. Seeded polymerization that reduces the duration of the lag phase and accelerates fibril growth is a widespread model to study amyloid formation. Seeding effects are hypothesized to be important in the "infectivity" of amyloids and are linked to the development of systemic amyloidosis in vivo. The exact mechanism of seeding is unclear yet critical to illuminating the propagation of amyloids. Here we report on the lateral and axial fragmentation of seed fibrils in the presence of lysozyme monomers at short time scales, followed by the generation of oligomers and growth of fibrils.

Details

Original languageEnglish
Pages (from-to)6880-6886
Number of pages7
JournalAnalytical Chemistry
Volume91
Issue number10
Early online date19 Apr 2019
Publication statusPublished - 21 May 2019