| AVS 62nd International Symposium & Exhibition | |
| Nanometer-scale Science and Technology | Monday Sessions |
| Session NS+AS+SP-MoA |
| Session: | Optical Spectroscopy at the Nanoscale |
| Presenter: | Francesco Simone Ruggeri, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland |
| Authors: | F.S. Ruggeri, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland T. Muller, University of Cambridge, UK D. Galante, CNR, Italy T.P.J. Knowles, University of Cambridge, UK H. Lashuel, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland C. D'Arrigo, CNR, Italy G. Dietler, Ecole Polytechnique Fédérale de Lausanne (EPFL), Switzerland |
| Correspondent: | Click to Email |
Aging of world population has increased the onset of several neurodegenerative disorders (ND). These diseases are connected with insoluble fibrillar proteins aggregates, termed Amyloid. During their aggregation, starting monomeric proteins undergo internal structural rearrangement bringing to fibrils with a final universal cross β-sheet quaternary structure. This structure is independent by the monomeric initial one and it is the fingerprint of amyloid and related diseases. Previously, the final fibrillar cross-β sheet structures were considered the cause of the illnesses. Nowadays, there is strong evidence that the intermediate oligomeric stages of fibrillation could be the cytotoxic one and most of the research groups are investigating the early stages of fibrillation and the inter-conversion of monomers into fibrils. Infrared spectroscopy is a key method for studying conformational properties of proteins and their structural conversion during amyloid fibrillation. Unfortunately, this and others bulk techniques are just able to give average information of the heterogeneous aggregating amyloid solution. To study the chemical structure of amyloid species at the nanoscale, we utilized a thermomechanical detection technique based on atomic force microscopy (nanoIR). If an IR pulse is absorbed by a sample, the local temperature rises and leads to a local thermal expansion. This deformation excites mechanical resonances of the AFM cantilever, in contact with the sample, allowing simultaneously acquiring topography, nanoscale chemical IR maps and/or spectra. We focused on the study of different amyloidogenic proteins, as α-synuclein, lysozyme and αβ42. We measured chemical spectra and IR maps of monomeric and fibrillar aggregates. For the first time, we distinguished chemically different amyloid structures at the single aggregate nanometer scale. Nanoscale chemical characterization of amyloidogenic structures as oligomers, protofibrils and fibrils 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 ND.