title: Mapping the Broad Structural and Mechanical Properties of Amyloid Fibrils.
abstract: Amyloids are fibrillar nanostructures of proteins that are assembled in several physiological processes in human cells (e.g., hormone storage) but also during the course of infectious (prion) and noninfectious (nonprion) diseases such as Creutzfeldt-Jakob and Alzheimer's diseases, respectively. How the amyloid state, a state accessible to all proteins and peptides, can be exploited for functional purposes but also have detrimental effects remains to be determined. Here, we measure the nanomechanical properties of different amyloids and link them to features found in their structure models. Specifically, we use shape fluctuation analysis and sonication-induced scission in combination with full-atom molecular dynamics simulations to reveal that the amyloid fibrils of the mammalian prion protein PrP are mechanically unstable, most likely due to a very low hydrogen bond density in the fibril structure. Interestingly, amyloid fibrils formed by HET-s, a fungal protein that can confer functional prion behavior, have a much higher Young's modulus and tensile strength than those of PrP, i.e., they are much stiffer and stronger due to a tighter packing in the fibril structure. By contrast, amyloids of the proteins RIP1/RIP3 that have been shown to be of functional use in human cells are significantly stiffer than PrP fibrils but have comparable tensile strength. Our study demonstrates that amyloids are biomaterials with a broad range of nanomechanical properties, and we provide further support for the strong link between nanomechanics and β-sheet characteristics in the amyloid core.
authors.affiliation: Michael Smith Laboratories-Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Guillaume
authors.initials: G
authors.lastname: Lamour
authors.affiliation: Michael Smith Laboratories-Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Roy
authors.initials: R
authors.lastname: Nassar
authors.affiliation: Michael Smith Laboratories-Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Patrick H W
authors.initials: PHW
authors.lastname: Chan
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Gunes
authors.initials: G
authors.lastname: Bozkurt
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts; State Key Laboratory of Genetic Engineering, Collaborative Innovation Center of Genetics and Development, School of Life Sciences, Fudan University, Shanghai, China.
authors.forename: Jixi
authors.initials: J
authors.lastname: Li
authors.affiliation: Michael Smith Laboratories-Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Bui
authors.affiliation: Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Calvin K
authors.initials: CK
authors.lastname: Yip
authors.affiliation: Michael Smith Laboratories-Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Thibault
authors.initials: T
authors.lastname: Mayor
authors.affiliation: Department of Chemistry, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Hongbin
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, and Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Michael Smith Laboratories-Centre for High-Throughput Biology, University of British Columbia, Vancouver, British Columbia, Canada; Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address: gsponer@msl.ubc.ca.
authors.forename: Jörg A
authors.initials: JA
authors.lastname: Gsponer
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D001696:Biomechanical Phenomena; D006801:Humans; D006860:Hydrogen Bonding; D007328:Insulin / Q000737:chemistry; D055595:Mechanical Phenomena; D056004:Molecular Dynamics Simulation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid; D007328:Insulin