Research offers clues to Alzheimer’s plaques (continued)

Detangling the fibrils
Researchers replaced certain carbon atoms in the peptides with the slightly radioactive isotope carbon-13. A sample of the material was immersed in a static magnetic field and exposed to a second, oscillating magnetic field. Carbon-13 nuclei in the sample resonated with the second field, emitting radio waves that were used to map their locations within the sample. NMR allowed researchers to measure the distances between carbon atoms within two-tenths of an angstrom (one ten-millionth of a millimeter).

With these distances known, they could deduce the three-dimensional structure of the entire b-amyloid fibril—the largest noncrystalline structure ever characterized.

After the researchers had determined the basic molecular structure of the peptide chains, they wanted some insight into the self-assembly process.

Small-angle neutron scattering at Argonne’s Intense Pulsed Neutron Source (IPNS) provided the higher resolution needed. For this study, Thiyagarajan joined with chemistry and pathology departments at the University of Chicago. Peptide samples were immersed in neutron beams from the IPNS, revealing the fibrils’ atomic structure.

Results showed that six of the peptide ribbons are laminated together, 10 angstroms apart—about the width of three atoms,—by weak bonding between corresponding hydrogen atoms along each peptide molecule. These strands gently twist in a clockwise direction to form the helical structures seen in electron micrographs. These strands are the “backbone atom” of the b-amyloid fibrils, Thiyagarajan said.

The researchers also found that pH—or acidity—has a strong effect on fibril formation: the higher the pH, the faster they form.

Additional studies were performed at the Basic Energy Sciences Synchrotron Radiation Center beamline at Argonne’s Advanced Photon Source.

New nanomaterials
This research may lead to new nanomaterials. Consisting of particles of a few hundred to a few thousand atoms, nanomaterials have heightened properties compared to bulk materials of the same composition.

In a modified form of the amyloid peptides studied at Argonne and the University of Chicago, zinc ions—atoms stripped of one or more electrons—were used to trigger the self-assembly process. Materials scientists are interested in this “nucleation” effect, which could allow nanomaterials to self-assemble into useful structures.

For more information, please contact David Jacqué.

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