Nanomechanics and intermolecular forces of amyloid revealed by four-dimensional electron microscopy

Author:

Fitzpatrick Anthony W. P.,Vanacore Giovanni M.,Zewail Ahmed H.

Abstract

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.

Funder

National Science Foundation

DOD | Air Force Office of Scientific Research

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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