title: Inhibition of protein aggregation by zwitterionic polymer-based core-shell nanogels.
abstract: Protein aggregation is a process by which misfolded proteins polymerizes into aggregates and forms fibrous structures with a β-sheet conformation, known as amyloids. It is an undesired outcome, as it not only causes numerous neurodegenerative diseases, but is also a major deterrent in the development of protein biopharmaceuticals. Here, we report a rational design for the synthesis of novel zwitterionic polymer-based core-shell nanogels via controlled radical polymerization. Nanogels with different sizes and functionalities in the core and shell were prepared. The nanogels exhibit remarkable efficiency in the protection of lysozyme against aggregation. Addition of nanogels suppresses the formation of toxic fibrils and also enables lysozyme to retain its enzymatic activity. Increasing the molecular weight and degree of hydrophobicity markedly increases its overall efficiency. Investigation of higher order structures revealed that lysozyme when heated without any additive loses its secondary structure and transforms into a random coil conformation. In contrast, presence of nanogels facilitates the retention of higher order structures by acting as molecular chaperones, thereby reducing molecular collisions. The present study is the first to show that it is possible to design zwitterionic nanogels using appropriate polymerization techniques that will protect proteins under conditions of extreme stress and inhibit aggregation.
authors.affiliation: School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa, 923-1292, Japan.
authors.forename: Robin
authors.initials: R
authors.lastname: Rajan
authors.affiliation: School of Materials Science, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa, 923-1292, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Matsumura
mesh_terms: D000682:Amyloid / Q000737:chemistry; D006358:Hot Temperature; D057927:Hydrophobic and Hydrophilic Interactions; D008689:Methacrylates; D046529:Microscopy, Electron, Transmission; D018832:Molecular Chaperones; D009113:Muramidase / Q000737:chemistry*; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011108:Polymers / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D008689:Methacrylates; D018832:Molecular Chaperones; D011108:Polymers; C016285:butyl methacrylate monomer; D009113:Muramidase