title: A kinetic study of ovalbumin fibril formation: the importance of fragmentation and end-joining.
abstract: The ability to control the morphologies of biomolecular aggregates is a central objective in the study of self-assembly processes. The development of predictive models offers the surest route for gaining such control. Under the right conditions, proteins will self-assemble into fibers that may rearrange themselves even further to form diverse structures, including the formation of closed loops. In this study, chicken egg white ovalbumin is used as a model for the study of fibril loops. By monitoring the kinetics of self-assembly, we demonstrate that loop formation is a consequence of end-to-end association between protein fibrils. A model of fibril formation kinetics, including end-joining, is developed and solved, showing that end-joining has a distinct effect on the growth of fibrillar mass density (which can be measured experimentally), establishing a link between self-assembly kinetics and the underlying growth mechanism. These results will enable experimentalists to infer fibrillar morphologies from an appropriate analysis of self-assembly kinetic data.
authors.affiliation: School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK; School of Chemistry, University of Edinburgh, Edinburgh, UK.
authors.forename: Jason M D
authors.initials: JM
authors.lastname: Kalapothakis
authors.affiliation: School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Morris
authors.affiliation: School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
authors.forename: Juraj
authors.initials: J
authors.lastname: Szavits-Nossan
authors.affiliation: School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
authors.forename: Kym
authors.initials: K
authors.lastname: Eden
authors.affiliation: School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
authors.forename: Sam
authors.initials: S
authors.lastname: Covill
authors.affiliation: School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
authors.forename: Sean
authors.initials: S
authors.lastname: Tabor
authors.affiliation: School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
authors.forename: Jay
authors.initials: J
authors.lastname: Gillam
authors.affiliation: School of Chemistry, The University of Manchester, Manchester, UK.
authors.forename: Perdita E
authors.initials: PE
authors.lastname: Barran
authors.affiliation: School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK.
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Allen
authors.affiliation: School of Physics and Astronomy, University of Edinburgh, Edinburgh, UK. Electronic address: cait.macphee@ed.ac.uk.
authors.forename: Cait E
authors.initials: CE
authors.lastname: MacPhee
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D000818:Animals; D002645:Chickens; D007700:Kinetics; D010047:Ovalbumin / Q000737:chemistry*; D058105:Polymerization
chemical_list: D000682:Amyloid; D010047:Ovalbumin