Trifluoroethanol modulates α-synuclein amyloid-like aggregate formation, stability and dissolution Maria Giovanna Di Carlo a , Valeria Vetri a,b, *, Gianpiero Buscarino a , Maurizio Leone a,b , Bente Vestergaard c , Vito Foderà c,d, ⁎ a Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle Scienze, Edificio 18, 90128 Palermo, Italy b Advanced Technologies Network Center, Università degli Studi di Palermo, Palermo, Italy c Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark d Section for Biologics, Department of Pharmacy, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark HIGHLIGHTS • Disassembly of αSN fibrils is triggered by changes in TFE concentration. • High TFE concentrations stabilize amy- loid-like aggregates. • A disassembly process could result in a release of non native oligomers. GRAPHICAL ABSTRACT abstract article info Article history: Received 9 March 2016 Received in revised form 13 June 2016 Accepted 20 June 2016 Available online 25 June 2016 The conversion of proteins into amyloid fibrils and other amyloid-like aggregates is closely connected to the onset of a series of age-related pathologies. Upon changes in environmental conditions, amyloid-like aggregates may also undergo disassembly into oligomeric aggregates, the latter being recognized as key effectors in toxicity. This indicates new possible routes for in vivo accumulation of toxic species. In the light of the recognized impli- cation of α-Synuclein (αSN) in Parkinson's disease, we present an experimental study on supramolecular assem- bly of αSN with a focus on stability and disassembly paths of such supramolecular aggregate species. Using spectroscopic techniques, two-photon microscopy, small-angle X-ray scattering and atomic force microscopy, we report evidences on how the stability of αSN amyloid-like aggregates can be altered by changing solution conditions. We show that amyloid-like aggregate formation can be induced at high temperature in the presence of trifluoroethanol (TFE). Moreover, sudden disassembly or further structural reorganisation toward higher Biophysical Chemistry 216 (2016) 23–30 ⁎ Corresponding authors at: Department of Pharmacy, University of Copenhagen (VF), Dipartimento di Fisica e Chimica, Università degli Studi di Palermo (VV). E-mail addresses: valeria.vetri@unipa.it (V. Vetri), vito.fodera@sund.ku.dk (V. Foderà). http://dx.doi.org/10.1016/j.bpc.2016.06.003 0301-4622/© 2016 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Biophysical Chemistry journal homepage: http://www.elsevier.com/locate/biophyschem