Biophysical Society Thematic Meeting - October 25-30, 2015

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.In our 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

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