title: Revealing molecular-level surface structure of amyloid fibrils in liquid by means of frequency modulation atomic force microscopy.
abstract: We have investigated the surface structure of islet amyloid polypeptide (IAPP) fibrils and α-synuclein protofibrils in liquid by means of frequency modulation atomic force microscopy (FM-AFM). Ångström-resolution FM-AFM imaging of isolated macromolecules in liquid is demonstrated for the first time. Individual β-strands aligned perpendicular to the fibril axis with a spacing of 0.5 nm are resolved in FM-AFM images, which confirms cross-β structure of IAPP fibrils in real space. FM-AFM images also reveal the existence of 4 nm periodic domains along the axis of IAPP fibrils. Stripe features with 0.5 nm spacing are also found in images of α-synuclein protofibrils. However, in contrast to the case for IAPP fibrils, the stripes are oriented 30° from the axis, suggesting the possibility of β-strand alignment in protofibrils different from that in mature fibrils or the regular arrangement of thioflavin T molecules present during the fibril preparation aligned at the surface of the protofibrils.
authors.affiliation: Frontier Science Organization, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukuma
authors.forename: Anika S
authors.initials: AS
authors.lastname: Mostaert
authors.forename: Louise C
authors.initials: LC
authors.lastname: Serpell
authors.forename: Suzanne P
authors.initials: SP
authors.lastname: Jarvis