Environmental Control of Amyloid Polymorphism by Modulation of Hydrodynamic Stress

Jiangtao Zhou, Leonardo Venturelli, Ludovic Keiser, Sergey K. Sekatskii, François Gallaire, Sandor Kasas, Giovanni Longo, Tuomas P.J. Knowles, Francesco S. Ruggeri*, Giovanni Dietler*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The phenomenon of amyloid polymorphism is a key feature of protein aggregation. Unravelling this phenomenon is of great significance for understanding the underlying molecular mechanisms associated with neurodegenerative diseases and for the development of amyloid-based functional biomaterials. However, the understanding of the molecular origins and the physicochemical factors modulating amyloid polymorphs remains challenging. Herein, we demonstrate an association between amyloid polymorphism and environmental stress in solution, induced by an air/water interface in motion. Our results reveal that low-stress environments produce heterogeneous amyloid polymorphs, including twisted, helical, and rod-like fibrils, whereas high-stress conditions generate only homogeneous rod-like fibrils. Moreover, high environmental stress converts twisted fibrils into rod-like fibrils both in-pathway and after the completion of mature amyloid formation. These results enrich our understanding of the environmental origin of polymorphism of pathological amyloids and shed light on the potential of environmentally controlled fabrication of homogeneous amyloid biomaterials for biotechnological applications.

Original languageEnglish
Pages (from-to)944-953
JournalACS Nano
Volume15
Issue number1
Early online date22 Dec 2020
DOIs
Publication statusPublished - Jan 2021

Keywords

  • air-water interface
  • amyloid polymorphism
  • environmental control
  • hydrodynamic flow
  • protein aggregation

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