Water molecular system dynamics associated with amyloidogenic nucleation as revealed by real time near infrared spectroscopy and aquaphotomics
The formation of amyloid fibrils proceeds via a nucleation-dependent mechanism in which nucleation phase is generally associated with a high free energy resulting in the rate-limiting step. On the basis of this kinetic feature, the nucleation is one of the most crucial phases controlling the pathoge...
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Published in | PloS one Vol. 9; no. 7; p. e101997 |
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Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
United States
Public Library of Science
11.07.2014
Public Library of Science (PLoS) |
Subjects | |
Online Access | Get full text |
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Summary: | The formation of amyloid fibrils proceeds via a nucleation-dependent mechanism in which nucleation phase is generally associated with a high free energy resulting in the rate-limiting step. On the basis of this kinetic feature, the nucleation is one of the most crucial phases controlling the pathogenesis of amyloidoses, but little is known about the details of how protein molecules and surrounding environment vary at this stage. Here, we applied near infrared (NIR) spectral monitoring of water structural changes in real time during the nucleation-dependent fibrillation of insulin. Whilst multivariate spectral analysis in the 2050-2350 nm spectral region indicated cross-β formation, characteristic transformations of water structure have been detected in the spectral region 1300-1600 nm corresponding to the first overtone of water OH stretching vibrations. Furthermore, specific water spectral patterns (aquagrams) related to different water molecular conformations have been found along the course of protein nucleation and aggregation. Right in the beginning, dissociation of hydrogen-bonded network in bulk water and coinstantaneous protein and ion hydration were observed, followed by water hydrogen-bonded networks development, presumably forcing the nucleation. These specific transformations of water spectral pattern could be used further as a biomarker for early non-invasive diagnosis of amyloidoses prior to explosive amplification and deposits of amyloid fibrils. |
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Bibliography: | Conceived and designed the experiments: EC RT. Performed the experiments: EC YT YM. Analyzed the data: YT RT. Contributed reagents/materials/analysis tools: EC YT YM RT. Contributed to the writing of the manuscript: EC RT. Competing Interests: The authors have declared that no competing interests exist. |
ISSN: | 1932-6203 1932-6203 |
DOI: | 10.1371/journal.pone.0101997 |