title: Nanomechanical properties of distinct fibrillar polymorphs of the protein α-synuclein.
abstract: Alpha-synuclein (α-Syn) is a small presynaptic protein of 140 amino acids. Its pathologic intracellular aggregation within the central nervous system yields protein fibrillar inclusions named Lewy bodies that are the hallmarks of Parkinson's disease (PD). In solution, pure α-Syn adopts an intrinsically disordered structure and assembles into fibrils that exhibit considerable morphological heterogeneity depending on their assembly conditions. We recently established tightly controlled experimental conditions allowing the assembly of α-Syn into highly homogeneous and pure polymorphs. The latter exhibited differences in their shape, their structure but also in their functional properties. We have conducted an AFM study at high resolution and performed a statistical analysis of fibrillar α-Syn shape and thermal fluctuations to calculate the persistence length to further assess the nanomechanical properties of α-Syn polymorphs. Herein, we demonstrated quantitatively that distinct polymorphs made of the same protein (wild-type α-Syn) show significant differences in their morphology (height, width and periodicity) and physical properties (persistence length, bending rigidity and axial Young's modulus).
authors.affiliation: Institut Galien Paris-Sud, CNRS, Univ. Paris-Sud, University Paris-Saclay, 92296 Châtenay-Malabry, France.
authors.forename: Ali
authors.initials: A
authors.lastname: Makky
authors.affiliation: Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Bousset
authors.affiliation: Luxembourg Institute of Science and Technology (LIST), Materials Research and Technology (MRT), L-4422 Belvaux, Luxembourg.
authors.forename: Jérôme
authors.initials: J
authors.lastname: Polesel-Maris
authors.affiliation: Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay, 91190 Gif-sur-Yvette, France.
authors.forename: Ronald
authors.initials: R
authors.lastname: Melki
mesh_terms: D055119:Elastic Modulus; D010300:Parkinson Disease / Q000378:metabolism; D066263:Protein Aggregation, Pathological; D020836:Protein Structure, Quaternary; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: C497604:SNCA protein, human; D051844:alpha-Synuclein