title: Strong interactions with polyethylenimine-coated human serum albumin nanoparticles (PEI-HSA NPs) alter α-synuclein conformation and aggregation kinetics.
abstract: The interaction between nanoparticles (NPs) and the small intrinsically disordered protein α-synuclein (αSN), whose aggregation is central in the development of Parkinson's disease, is of great relevance in biomedical applications of NPs as drug carriers. Here we showed using a combination of different techniques that αSN interacts strongly with positively charged polyethylenimine-coated human serum albumin (PEI-HSA) NPs, leading to a significant alteration in the αSN secondary structure. In contrast, the weak interactions of αSN with HSA NPs allowed αSN to remain unfolded. These different levels of interactions had different effects on αSN aggregation. While the weakly interacting HSA NPs did not alter the aggregation kinetic parameters of αSN, the rate of primary nucleation increased in the presence of PEI-HSA NPs. The aggregation rate changed in a PEI-HSA NP-concentration dependent and size independent manner and led to fibrils which were covered with small aggregates. Furthermore, PEI-HSA NPs reduced the level of membrane-perturbing oligomers and reduced oligomer toxicity in cell assays, highlighting a potential role for NPs in reducing αSN pathogenicity in vivo. Collectively, our results highlight the fact that a simple modification of NPs can strongly modulate interactions with target proteins, which may have important and positive implications in NP safety.
authors.affiliation: Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, DK - 8000 Aarhus C, Denmark. dao@inano.au.dk and Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115-143, Tehran, Iran.
authors.forename: Hossein
authors.initials: H
authors.lastname: Mohammad-Beigi
authors.affiliation: Biotechnology Group, Faculty of Chemical Engineering, Tarbiat Modares University, P.O. Box 14115-143, Tehran, Iran.
authors.forename: Seyed Abbas
authors.initials: SA
authors.lastname: Shojaosadati
authors.affiliation: Department of Biomedicine, Aarhus University, 8000 Aarhus C, Denmark.
authors.forename: Amir Tayaranian
authors.initials: AT
authors.lastname: Marvian
authors.affiliation: Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, DK - 8000 Aarhus C, Denmark. dao@inano.au.dk.
authors.forename: Jannik Nedergaard
authors.initials: JN
authors.lastname: Pedersen
authors.affiliation: Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, DK - 8000 Aarhus C, Denmark.
authors.forename: Lasse Hyldgaard
authors.initials: LH
authors.lastname: Klausen
authors.affiliation: Department of Biomedicine-Medical Microbiology and Immunology, Aarhus University, 8000 Aarhus C, Denmark.
authors.forename: Gunna
authors.initials: G
authors.lastname: Christiansen
authors.affiliation: Interdisciplinary Nanoscience Centre (iNANO) and Department of Chemistry, Aarhus University, Gustav Wieds Vej 14, DK - 8000 Aarhus C, Denmark.
authors.forename: Jan Skov
authors.initials: JS
authors.lastname: Pedersen
authors.affiliation: Interdisciplinary Nanoscience Centre (iNANO), Aarhus University, Gustav Wieds Vej 14, DK - 8000 Aarhus C, Denmark.
authors.forename: Mingdong
authors.initials: M
authors.lastname: Dong
authors.affiliation: Department of Industrial and Environmental Biotechnology, National Institute of Genetic Engineering and Biotechnology, P.O. Box: 1417863171, Tehran, Iran. morshedi@nigeb.ac.ir.
authors.forename: Dina
authors.initials: D
authors.lastname: Morshedi
authors.affiliation: Interdisciplinary Nanoscience Centre (iNANO) and Department of Molecular Biology and Genetics, Aarhus University, Gustav Wieds Vej 14, DK - 8000 Aarhus C, Denmark. dao@inano.au.dk.
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Otzen
mesh_terms: D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D011094:Polyethyleneimine / Q000737:chemistry*; D066329:Protein Aggregates; D012709:Serum Albumin / Q000737:chemistry*; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D066329:Protein Aggregates; C497604:SNCA protein, human; D012709:Serum Albumin; D051844:alpha-Synuclein; D011094:Polyethyleneimine