Hydration Profiles of Amyloidogenic Molecular Structures |
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Authors: | Florin Despa Ariel Fernández L Ridgway Scott R Stephen Berry |
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Institution: | (1) Department of Pharmacology, University of California, Davis, CA 95616, USA;(2) Department of Bioengineering, Rice University, Houston, TX 77251, USA;(3) Department of Computer Science, The University of Chicago, Chicago, IL 60637, USA;(4) Department of Mathematics, The University of Chicago, Chicago, IL 60637, USA;(5) Institute for Biophysical Dynamics, The University of Chicago, Chicago, IL 60637, USA;(6) Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA |
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Abstract: | 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. |
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Keywords: | Protein hydration Protein aggregation Amyloids Alzheimer’ s disease Conformational diseases Biological water Magnetic resonance imaging |
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