title: Morphology and mechanical properties of multi-stranded amyloid fibrils probed by atomistic and coarse-grained simulations.
abstract: Amyloid fibrils are responsible for pathogenesis of various diseases and exhibit the structural feature of an ordered, hierarchical structure such as multi-stranded helical structure. As the multi-strandedness of amyloid fibrils has recently been found to be highly correlated with their toxicity and infectivity, it is necessary to study how the hierarchical (i.e. multi-stranded) structure of amyloid fibril is formed. Moreover, although it has recently been reported that the nanomechanics of amyloid proteins plays a key role on the amyloid-induced pathogenesis, a critical role that the multi-stranded helical structure of the fibrils plays in their nanomechanical properties has not fully characterized. In this work, we characterize the morphology and mechanical properties of multi-stranded amyloid fibrils by using equilibrium molecular dynamics simulation and elastic network model. It is shown that the helical pitch of multi-stranded amyloid fibril is linearly proportional to the number of filaments comprising the amyloid fibril, and that multi-strandedness gives rise to improving the bending rigidity of the fibril. Moreover, we have also studied the morphology and mechanical properties of a single protofilament (filament) in order to understand the effect of cross-β structure and mutation on the structures and mechanical properties of amyloid fibrils. Our study sheds light on the underlying design principles showing how the multi-stranded amyloid fibril is formed and how the structure of amyloid fibrils governs their nanomechanical properties.
authors.affiliation: Department of Mechanical Engineering, Korea University, Seoul 02841, Korea. Department of Mechanical Engineering, Boston University, Boston, MA 02115, USA.
authors.forename: Gwonchan
authors.initials: G
authors.lastname: Yoon
authors.forename: Myeongsang
authors.initials: M
authors.lastname: Lee
authors.forename: Kyungwoo
authors.initials: K
authors.lastname: Kim
authors.forename: Jae In
authors.initials: JI
authors.lastname: Kim
authors.forename: Hyun Joon
authors.initials: HJ
authors.lastname: Chang
authors.forename: Inchul
authors.initials: I
authors.lastname: Baek
authors.forename: Kilho
authors.initials: K
authors.lastname: Eom
authors.forename: Sungsoo
authors.initials: S
authors.lastname: Na
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D001696:Biomechanical Phenomena; D056004:Molecular Dynamics Simulation
chemical_list: D000682:Amyloid