title: Polymorphism of amyloid β peptide in different environments: implications for membrane insertion and pore formation.
abstract: Amyloid-β (Aβ) peptides are thought to be involved in neurodegenerative diseases such as Alzheimer's disease and Down's syndrome. They form a large number of polymorphic structures, including heterogeneous ionic pores in membranes as well as different types of fibrillar and globular structures on surfaces and in solution. Understanding the origin of these structures and the factors that influence their occurrence is of great biomedical interest because of the possible relationship between structure and pathogenicity. Here, we use atomic force microscopy (AFM) and molecular dynamics (MD) simulations to demonstrate that at room temperature a truncated Aβ peptide which is generated in vivo and shown to be toxic in vitro forms fibrillar structures on hydrophobic graphite surfaces, but not on hydrophilic mica or lipid bilayers. Our results suggest that the toxic pores and fibrillar polymorphic organizations can be explained in terms of the U-shaped β-strand-turn-β-strand structural motif observed for full length Aβ and other amyloids, as well as the physicochemical properties at the interfaces. The interactions of the hydrophobic, truncated Aβ with its environment illustrate that the universal amyloid motif can provide a link between the pore and fibrillar structures and indicate that surfaces with different physicochemical properties can shift the polymorphic landscape toward other conformational states.
authors.affiliation: Department of Bioengineering and Department of Mechanical and Aerospace Engineering, University of California, San Diego, La Jolla, CA 92093, U.S.A.
authors.forename: Fernando Terán
authors.initials: FT
authors.lastname: Arce
authors.forename: Hyunbum
authors.initials: H
authors.lastname: Jang
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Preston B
authors.initials: PB
authors.lastname: Landon
authors.forename: Ruth
authors.initials: R
authors.lastname: Nussinov
authors.forename: Ratnesh
authors.initials: R
authors.lastname: Lal