Hydration profiles of amyloidogenic molecular structures

Florin Despa, Ariel Fernández, L. Ridgway Scott, R. Stephen Berry

Research output: Contribution to journalArticlepeer-review

7 Scopus citations


Hydration shells of normal proteins display regions of highly structured water as well as patches of less structured bulk-like water. Recent studies suggest that isomers with larger surface densities of patches of bulk-like water have an increased propensity to aggregate. These aggregates are toxic to the cellular environment. Hence, the early detection of these toxic deposits is of paramount medical importance. We show that various morphological states of association of such isomers can be differentiated from the normal protein background based on the characteristic partition between bulk, caged, and surface hydration water and the magnetic resonance (MR) signals of this water. We derive simple mathematical equations relating the compartmentalization of water to the local hydration fraction and the packing density of the newly formed molecular assemblies. Then, we employ these equations to predict the MR response of water constrained by protein aggregation. Our results indicate that single units and compact aggregates that contain no water between constituents induce a shift of the MR signal from normal protein background to values in the hyperintensity domain (bright spots), corresponding to bulk water. In contrast, large plaques that cage significant amounts of water between constituents are likely to generate MR responses in the hypointensity domain (dark spots), typical for strongly correlated water. The implication of these results is that amyloids can display both dark and bright spots when compared to the normal gray background tissue on MR images. In addition, our findings predict that the bright spots are more likely to correspond to amyloids in their early stage of development. The results help explain the MR contrast patterns of amyloids and suggest a new approach for identifying unusual protein aggregation related to disease.

Original languageEnglish
Pages (from-to)577-590
Number of pages14
JournalJournal of Biological Physics
Issue number6
StatePublished - Dec 2008

Bibliographical note

Funding Information:
Acknowledgements F.D. acknowledges that part of this work was done at the John von Neumann Institute for Computing, Research Center Jülich, Germany. The research of A.F. is supported by NIH grant R01-GM072614. L.R.S. would like to acknowledge support from the Institute for Biophysical Dynamics at the University of Chicago.


  • Alzheimer's disease
  • Amyloids
  • Biological water
  • Conformational diseases
  • Magnetic resonance imaging
  • Protein aggregation
  • Protein hydration

ASJC Scopus subject areas

  • Biophysics
  • Atomic and Molecular Physics, and Optics
  • Molecular Biology
  • Cell Biology


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