title: Complexation of amyloid fibrils with charged conjugated polymers.
abstract: It has been suggested that conjugated charged polymers are amyloid imaging agents and promising therapeutic candidates for neurological disorders. However, very less is known about their efficacy in modulating the amyloid aggregation pathway. Here, we studied the modulation of Parkinson's disease associated α-synuclein (AS) amyloid assembly kinetics using conjugated polyfluorene polymers (PF, cationic; PFS, anionic). We also explored the complexation of these charged polymers with the various AS aggregated species including amyloid fibrils and oligomers using multidisciplinary biophysical techniques. Our data suggests that both polymers irrespective of their different charges in the side chains increase the fibrilization kinetics of AS and also remarkably change the morphology of the resultant amyloid fibrils. Both polymers were incorporated/aligned onto the AS amyloid fibrils as evident from electron microscopy (EM) and atomic force microscopy (AFM), and the resultant complexes were structurally distinct from their pristine form of both polymers and AS supported by FTIR study. Additionally, we observed that the mechanism of interactions between the polymers with different species of AS aggregates were markedly different.
authors.affiliation: Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay , Mumbai, Maharashtra, Mumbai 400076, India.
authors.forename: Dhiman
authors.initials: D
authors.lastname: Ghosh
authors.forename: Paulami
authors.initials: P
authors.lastname: Dutta
authors.forename: Chanchal
authors.initials: C
authors.lastname: Chakraborty
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Singh
authors.forename: A
authors.initials: A
authors.lastname: Anoop
authors.forename: Narendra Nath
authors.initials: NN
authors.lastname: Jha
authors.forename: Reeba S
authors.initials: RS
authors.lastname: Jacob
authors.forename: Mrityunjoy
authors.initials: M
authors.lastname: Mondal
authors.forename: Shruti
authors.initials: S
authors.lastname: Mankar
authors.forename: Subhadeep
authors.initials: S
authors.lastname: Das
authors.forename: Sudip
authors.initials: S
authors.lastname: Malik
authors.forename: Samir K
authors.initials: SK
authors.lastname: Maji
mesh_terms: D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D052160:Benzothiazoles; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D005465:Fluorocarbon Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D015870:Gene Expression; D006801:Humans; D007700:Kinetics; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D066329:Protein Aggregates; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013844:Thiazoles; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics
chemical_list: D000682:Amyloid; D052160:Benzothiazoles; D005465:Fluorocarbon Polymers; D066329:Protein Aggregates; D011994:Recombinant Proteins; D012996:Solutions; D013844:Thiazoles; D051844:alpha-Synuclein; C009462:thioflavin T