Nanomechanics and intermolecular forces of amyloid revealed by four-dimensional electron microscopy.
The amyloid state of polypeptides is a stable, highly organized structural form consisting of laterally associated β-sheet protofilaments that may be adopted as an alternative to the functional, native state. Identifying the balance of forces stabilizing amyloid is fundamental to understanding the wide accessibility of this state to peptides and proteins with unrelated primary sequences, various chain lengths, and widely differing native structures. Here, we use four-dimensional electron microscopy to demonstrate that the forces acting to stabilize amyloid at the atomic level are highly anisotropic, that an optimized interbackbone hydrogen-bonding network within β-sheets confers 20 times more rigidity on the structure than sequence-specific sidechain interactions between sheets, and that electrostatic attraction of protofilaments is only slightly stronger than these weak amphiphilic interactions. The potential biological relevance of the deposition of such a highly anisotropic biomaterial in vivo is discussed.
['Fitzpatrick|Anthony W P|AW|', 'Vanacore|Giovanni M|GM|', 'Zewail|Ahmed H|AH|']
D000595:Amino Acid Sequence D000682:Amyloid D016880:Anisotropy D055592:Biophysical Phenomena D003198:Computer Simulation D003460:Crystallization D008854:Microscopy, Electron D053758:Nanoparticles D014961:X-Ray Diffraction
nanomechanics proteins 4D electron diffraction structural dynamics