Morphology and mechanical properties of multi-stranded amyloid fibrils probed by atomistic and coarse-grained simulations

Gwonchan Yoon, Myeongsang Lee, Kyungwoo Kim, Jae In Kim, Hyun Joon Chang, Inchul Baek, Kilho Eom, Sung Soo Na

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Amyloid fibrils are responsible for pathogenesis of various diseases and exhibit the structural feature of an ordered, hierarchical structure such as multi-stranded helical structure. As the multi-strandedness of amyloid fibrils has recently been found to be highly correlated with their toxicity and infectivity, it is necessary to study how the hierarchical (i.e. multi-stranded) structure of amyloid fibril is formed. Moreover, although it has recently been reported that the nanomechanics of amyloid proteins plays a key role on the amyloid-induced pathogenesis, a critical role that the multi-stranded helical structure of the fibrils plays in their nanomechanical properties has not fully characterized. In this work, we characterize the morphology and mechanical properties of multi-stranded amyloid fibrils by using equilibrium molecular dynamics simulation and elastic network model. It is shown that the helical pitch of multi-stranded amyloid fibril is linearly proportional to the number of filaments comprising the amyloid fibril, and that multi-strandedness gives rise to improving the bending rigidity of the fibril. Moreover, we have also studied the morphology and mechanical properties of a single protofilament (filament) in order to understand the effect of cross-β structure and mutation on the structures and mechanical properties of amyloid fibrils. Our study sheds light on the underlying design principles showing how the multi-stranded amyloid fibril is formed and how the structure of amyloid fibrils governs their nanomechanical properties.

Original languageEnglish
Article number066021
JournalPhysical Biology
Volume12
Issue number6
DOIs
Publication statusPublished - 2015 Dec 30

Keywords

  • amyloid proteins
  • molecular dynamics
  • multi-strandness
  • normal mode analysis

ASJC Scopus subject areas

  • Biophysics
  • Molecular Biology
  • Cell Biology
  • Structural Biology

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