Modulating amyloids’ formation path with sound energy

Anna Kozell, Dror Eliaz, Aleksei Solomonov, Doron Benyamin, Guy Shmul, Ori Brookstein, Irit Rosenhek-Goldian, Uri Raviv, Ulyana Shimanovich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Protein folding is crucial for biological activity. Proteins’ failure to fold correctly underlies various pathological processes, including amyloidosis, the aggregation of insoluble proteins (e.g., lysozymes) in organs. The exact conditions that trigger the structural transition of amyloids into β-sheet-rich aggregates are poorly understood, as is the case for the amyloidogenic self-assembly pathway. Ultrasound is routinely used to destabilize a protein’s structure and enhance amyloid growth. Here, we report on an unexpected ultrasound effect on lysozyme amyloid species at different stages of aggregation: ultrasound-induced structural perturbation gives rise to nonamyloidogenic folds. Our infrared and X-ray analyses of the chemical, mechanical, and thermal effects of sound on lysozyme’s structure found, in addition to the expected ultrasound-induced damage, evidence of irreversible disruption of the β-sheet fold of fibrillar lysozyme resulting in their structural transformation into monomers with no β-sheets. This structural transition is reflected in changes in the kinetics of protein self-assembly, namely, either prolonged nucleation or accelerated fibril growth. Using solution X-ray scattering, we determined the structure, the mass fraction of lysozyme monomer, and the morphology of its filamentous assemblies formed under different sound parameters. A nanomechanical analysis of ultrasound-modified protein assemblies revealed a correlation between the β-sheet content and elastic modulus of the protein material. Suppressing one of the ultrasound-derived effects allowed us to control the structural transformations of lysozyme. Overall, our comprehensive investigation establishes the boundary conditions under which ultrasound damages protein structure and fold. This knowledge can be utilized to impose medically desirable structural modifications on amyloid β-sheet-rich proteins.

Original languageAmerican English
Article numbere2212849120
JournalProceedings of the National Academy of Sciences of the United States of America
Volume120
Issue number3
DOIs
StatePublished - 17 Jan 2023

Bibliographical note

Publisher Copyright:
Copyright © 2023 the Author(s).

Keywords

  • amyloid
  • beta-sheet conformation
  • cavitation
  • fibrillar protein self-assembly
  • ultrasound

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