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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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Detalles Bibliográficos
Autores principales: Chatani, Eri, Tsuchisaka, Yutaro, Masuda, Yuki, Tsenkova, Roumiana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4094474/
https://www.ncbi.nlm.nih.gov/pubmed/25013915
http://dx.doi.org/10.1371/journal.pone.0101997
Descripción
Sumario: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.