title: Exceptional rigidity and biomechanics of amyloid revealed by 4D electron microscopy.
abstract: Amyloid is an important class of proteinaceous material because of its close association with protein misfolding disorders such as Alzheimer's disease and type II diabetes. Although the degree of stiffness of amyloid is critical to the understanding of its pathological and biological functions, current estimates of the rigidity of these β-sheet-rich protein aggregates range from soft (10(8) Pa) to hard (10(10) Pa) depending on the method used. Here, we use time-resolved 4D EM to directly and noninvasively measure the oscillatory dynamics of freestanding, self-supporting amyloid beams and their rigidity. The dynamics of a single structure, not an ensemble, were visualized in space and time by imaging in the microscope an amyloid-dye cocrystal that, upon excitation, converts light into mechanical work. From the oscillatory motion, together with tomographic reconstructions of three studied amyloid beams, we determined the Young modulus of these highly ordered, hydrogen-bonded β-sheet structures. We find that amyloid materials are very stiff (10(9) Pa). The potential biological relevance of the deposition of such a highly rigid biomaterial in vivo are discussed.
authors.affiliation: Physical Biology Center for Ultrafast Science and Technology, Arthur Amos Noyes Laboratory of Chemical Physics, California Institute of Technology, Pasadena, CA 91125, USA.
authors.forename: Anthony W P
authors.initials: AW
authors.lastname: Fitzpatrick
authors.forename: Sang Tae
authors.initials: ST
authors.lastname: Park
authors.forename: Ahmed H
authors.initials: AH
authors.lastname: Zewail
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000502:physiology / Q000648:ultrastructure*; D001696:Biomechanical Phenomena; D055119:Elastic Modulus; D055032:Electron Microscope Tomography; D006801:Humans; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D017433:Protein Structure, Secondary
chemical_list: D000682:Amyloid
keywords: cross-β structure; microcantilever; nanomechanics