title: Polymorphism of amyloid-like fibrils can be defined by the concentration of seeds.
abstract: Prions are infectious proteins where the same protein may express distinct strains. The strains are enciphered by different misfolded conformations. Strain-like phenomena have also been reported in a number of other amyloid-forming proteins. One of the features of amyloid strains is the ability to self-propagate, maintaining a constant set of physical properties despite being propagated under conditions different from those that allowed initial formation of the strain. Here we report a cross-seeding experiment using strains formed under different conditions. Using high concentrations of seeds results in rapid elongation and new fibrils preserve the properties of the seeding fibrils. At low seed concentrations, secondary nucleation plays the major role and new fibrils gain properties predicted by the environment rather than the structure of the seeds. Our findings could explain conformational switching between amyloid strains observed in a wide variety of in vivo and in vitro experiments.
authors.affiliation: Department of Biothermodynamics and Drug Design, Vilnius University, Institute of Biotechnology, Vilnius, Lithuania.
authors.forename: Tomas
authors.initials: T
authors.lastname: Sneideris
authors.affiliation: Department of Biothermodynamics and Drug Design, Vilnius University, Institute of Biotechnology, Vilnius, Lithuania.
authors.forename: Katažyna
authors.initials: K
authors.lastname: Milto
authors.affiliation: Department of Biothermodynamics and Drug Design, Vilnius University, Institute of Biotechnology, Vilnius, Lithuania.
authors.forename: Vytautas
authors.initials: V
authors.lastname: Smirnovas
keywords: Amyloid; Amyloid-like fibrils; Elongation; Nucleation; Polymorphism; Prion; Prion strain; Protein aggregation; Protein misfolding