title: Intrinsic structural heterogeneity and long-term maturation of amyloid β peptide fibrils.
abstract: Amyloid β peptides form fibrils that are commonly assumed to have a dry, homogeneous, and static internal structure. To examine these assumptions, fibrils under various conditions and different ages have been examined with multidimensional infrared spectroscopy. Each peptide in the fibril had a ¹³C═¹⁸O label in the backbone of one residue to disinguish the amide I' absorption due to that residue from the amide I' absorption of other residues. Fibrils examined soon after they formed, and reexamined after 1 year in the dry state, exhibited spectral changes confirming that structurally significant water molecules were present in the freshly formed fibrils. Results from fibrils incubated in solution for 4 years indicate that water molecules remained trapped within fibrils and mobile over the 4 year time span. These water molecules are structurally significant because they perturb the parallel β-sheet hydrogen bonding pattern at frequent intervals and at multiple points within individual fibrils, creating structural heterogeneity along the length of a fibril. These results show that the interface between β-sheets in an amyloid fibril is not a "dry zipper", and that the internal structure of a fibril evolves while it remains in a fibrillar state. These features, water trapping, structural heterogeneity, and structural evolution within a fibril over time, must be accommodated in models of amyloid fibril structure and formation.
authors.affiliation: Ultrafast Optical Processes Laboratory, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, United States.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Ma
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Komatsu
authors.forename: Yung Sam
authors.initials: YS
authors.lastname: Kim
authors.forename: Liu
authors.initials: L
authors.lastname: Liu
authors.forename: Robin M
authors.initials: RM
authors.lastname: Hochstrasser
authors.forename: Paul H
authors.initials: PH
authors.lastname: Axelsen
mesh_terms: D000577:Amides / Q000737:chemistry; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D006801:Humans; D013055:Spectrophotometry, Infrared / Q000379:methods; D013997:Time Factors; D014867:Water / Q000737:chemistry*
chemical_list: D000577:Amides; D016229:Amyloid beta-Peptides; D014867:Water