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Nat Commun. 2015 Jul 28;6:7831. doi: 10.1038/ncomms8831.

Infrared nanospectroscopy characterization of oligomeric and fibrillar aggregates during amyloid formation.

Author information

1
Laboratoire de Physique de la Matière Vivante, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
2
Department of Basic and Clinical Neuroscience, King's College, London, UK.
3
Institute of Nuclear Physics, Polish Academy of Sciences, 31-342 Krakow, Poland.

Abstract

Amyloids are insoluble protein fibrillar aggregates. The importance of characterizing their aggregation has steadily increased because of their link to human diseases and material science applications. In particular, misfolding and aggregation of the Josephin domain of ataxin-3 is implicated in spinocerebellar ataxia-3. Infrared nanospectroscopy, simultaneously exploiting atomic force microscopy and infrared spectroscopy, can characterize at the nanoscale the conformational rearrangements of proteins during their aggregation. Here we demonstrate that we can individually characterize the oligomeric and fibrillar species formed along the amyloid aggregation. We describe their secondary structure, monitoring at the nanoscale an α-to-β transition, and couple these studies with an independent measurement of the evolution of their intrinsic stiffness. These results suggest that the aggregation of Josephin proceeds from the monomer state to the formation of spheroidal intermediates with a native structure. Only successively, these intermediates evolve into misfolded aggregates and into the final fibrils.

PMID:
26215704
PMCID:
PMC4525161
DOI:
10.1038/ncomms8831
[Indexed for MEDLINE]
Free PMC Article

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