AFM reveals that hydrogen bonds govern amyloid structure

David L. Shenkenberg

Researchers from the University of Cambridge in the UK have used atomic force microscopy (AFM) and atomistic simulations to investigate the contribution of hydrogen bonds to the structure of amyloid fibrils. They discovered that hydrogen bonds are the glue that holds amyloid structure together.

They studied nine types of amyloid fibrils with various lengths, diverse native structures and dissimilar amino acid sequences, examining no less than 50 fibrils of each type and more than 900 fibrils in total. AFM was performed in tapping mode with an instrument from Agilent Technologies Inc. of Santa Clara, Calif.

The stiffness of the amyloids ranged across four orders of magnitude, or a factor of 10,000. The scientists stated that the AFM data conform to Young’s modulus of elasticity, and they used the classical equation to calculate that hydrogen bonding contributes to the rigidity more than any other factor, as detailed in the Dec. 21 issue of Science.

The researchers noted that, in contrast to other proteins, amyloids share common structural features yet have diverse amino acid sequences and are folded into native structures through various pathways. Amyloid structures have been found in bacterial coatings and in organisms as scaffolds for catalytic reactions, in addition to their well-known presence in the brains of patients with neurodegenerative disorders such as Alzheimer’s disease. Based on these previously obtained data and on the new hydrogen bonding data, the researchers concluded that amyloids comprise a generic class of proteins.

Amyloids have garnered interest as nanotechnology building blocks, and the scientists believe that understanding that hydrogen bonding governs amyloid structure will enable development of a multitude of such structures.