Sound-mediated nucleation and growth of amyloid fibrils

Anna Kozell, Aleksei Solomonov, Roman Gaidarov, Doron Benyamin, Irit Rosenhek-Goldian, Harry Mark Greenblatt, Yaakov Levy, Ariel Amir, Uri Raviv, Ulyana Shimanovich*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

Mechanical energy, specifically in the form of ultrasound, can induce pressure variations and temperature fluctuations when applied to an aqueous media. These conditions can both positively and negatively affect protein complexes, consequently altering their stability, folding patterns, and self-assembling behavior. Despite much scientific progress, our current understanding of the effects of ultrasound on the self-assembly of amyloidogenic proteins remains limited. In the present study, we demonstrate that when the amplitude of the delivered ultrasonic energy is sufficiently low, it can induce refolding of specific motifs in protein monomers, which is sufficient for primary nucleation; this has been revealed by MD. These ultrasound-induced structural changes are initiated by pressure perturbations and are accelerated by a temperature factor. Furthermore, the prolonged action of low-amplitude ultrasound enables the elongation of amyloid protein nanofibrils directly from natively folded monomeric lysozyme protein, in a controlled manner, until it reaches a critical length. Using solution X-ray scattering, we determined that nanofibrillar assemblies, formed either under the action of sound or from natively fibrillated lysozyme, share identical structural characteristics. Thus, these results provide insights into the effects of ultrasound on fibrillar protein self-assembly and lay the foundation for the potential use of sound energy in protein chemistry.

Original languageEnglish
Article numbere2315510121
Number of pages10
JournalProceedings of the National Academy of Sciences - PNAS
Volume121
Issue number34
Early online date12 Aug 2024
DOIs
Publication statusPublished - 20 Aug 2024

Funding

The authors acknowledge the European Synchrotron Radiation Facility (ESRF), beamline ID02 (T. Narayanan, L. Matthews, and the rest of the ID02 team) for providing use of the synchrotron radiation facility and for assistance in using the beamline. U.S. acknowledges financial support from the Gruber Foundation, the Nella and Leon Benoziyo Center for Neurological Diseases. In addition, U.S. thanks the Perlman family for funding the Shimanovich Lab at the Weizmann Institute of Science: “This research was made possible in part by the generosity of the Harold Perlman Family.” The authors would like to acknowledge partial support from the GMJ Schmidt Minerva Center of Supramolecular Architectures at the Weizmann Institute, the Mondry Family Fund for the University of Michigan/Weizmann collaboration, the Gerald Schwartz and Heather Reisman Foundation, and the WIS Sustainability and Energy Research Initiative (SAERI). This research was supported by a research grant from the Tom and Mary Beck Center for Advanced and Intelligent Materials at the Weizmann Institute of Science, Rehovot, Israel. Molecular graphics and analyses were performed with UCSF ChimeraX, developed by the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco, with support from National Institutes of Health R01-GM129325 and the Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases. A.A. thanks the Clore center for Biological Physics for their support. The authors are also grateful to Steve Manch for the English editing. Publisher Copyright: Copyright © 2024 the Author(s). Published by PNAS.

All Science Journal Classification (ASJC) codes

  • General

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