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Polymers and Self Assembly: From Biology to Nanomaterials
Tuesday Speaker Abstracts
Amyloids Structural and Nanomechanical Characterization at the Individual Aggregate
Scale
Francesco Simone Ruggeri
1
, Sophie Vieweg
2
, Giovanni Longo
1
, Annalisa Pastore
3
, Hilal
Lashuel
2
, Giovanni Dietler
1
.
1
École Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland,
3
King's College,
London, United Kingdom.
2
École Polytechnique Fédérale de Lausanne (EPFL), Lausanne,
Switzerland,
Aging of the population has increased the visibility of several neurodegenerative disorders such
as Parkinson’s and Ataxia diseases. Their onset is connected with insoluble fibrillar protein
aggregates, called amyloids. However, these structures were also discovered in many
physiologically beneficial roles (functional amyloids) including bacterial coatings and adhesives.
During their aggregation, monomeric proteins undergo internal structural rearrangements leading
to the formation of fibrils with a universal cross beta-sheet quaternary structure. This
conformation is independent of the monomeric initial structure and is the fingerprint of amyloids.
Strong evidence indicates that neurodegeneration is produced by the intermediate species of
fibrillization. This poses the problem of investigating the early stages of the inter-conversion of
monomers into amyloid
fibrils.Inour work, we investigated amyloids structural and mechanical
properties by single molecule Atomic Force Microscopy (AFM) based methods. Infrared
nanospectroscopy (nanoIR), simultaneously exploiting AFM and Infrared Spectroscopy, can
characterize at the individual aggregate scale the conformational rearrangements of proteins
during their aggregation. Whereas, AFM Quantitative Imaging can map the nanomechanical
properties of amyloid aggregates at the nanoscale. In this way, we correlate the secondary
structure of amyloid intermediates and final aggregates to their nanomechanical properties. Our
results directly demonstrate, for the first time at the individual amyloid species scale, that the
increase of beta-sheet content is a fundamental parameter determining the growth of amyloids
intrinsic stiffness.[1]Nanoscale chemical characterization of amyloidogenic structures is central
to understand how proteins misfold and aggregate, to unravel the structural rearrangement of
monomers inside amyloid fibrils and to target pharmacological approach to neurodegenerative
disorders. Finally, it is central to measure and quantify the ultra-structural properties of amyloid
fibrils in order to appreciate their full potential as biomaterials.1 Ruggeri, Nat. Commun., 2015