Compressibility of insulin amyloid fibrils determined by X-ray diffraction in a diamond anvil cell

Abstract

Amyloid fibrils are fibrous structures that originate from the self-assembly of polypeptides. Their formation is linked to debilitating diseases associated with protein misfolding, including Alzheimer's disease and type-II diabetes. In recent years, it has been suggested that such protein and polypeptide fibrils might provide useful novel nanomaterials. Here, we present the results of a study on the high pressure stability and compressibility of mature amyloid fibrils of insulin by synchrotron X-ray diffraction in a diamond anvil cell. The diffraction results allow a direct estimation of the elastic modulus and the corresponding compression of the cross-β structure along the fiber axis. The average hydrogen bond compressibility is comparable to that in native proteins, suggesting that the fibrils are well-packed.

Keywords:

• amyloid fibril
• X-ray diffraction
• insulin
• diamond anvil cell
• elastic modulus

Acknowledgements

We thank Swiss-Norwegian Beamline at ESRF for access to the beamline. F.M. is a postdoctoral research fellow of the Research Foundation Flanders (FWO-Vlaanderen). R.Q.C. and P.F.M. are supported by EPSRC Portfolio grant EP/D504872 (to P.F.M., C.R.A. Catlow and P. Barnes) and EPSRC Senior Research Fellowship EP/D07357X (PFM).