AUTHOR=Grasso Gianvito , Rebella Martina , Morbiducci Umberto , Tuszynski Jack A. , Danani Andrea , Deriu Marco A. 

TITLE=The Role of Structural Polymorphism in Driving the Mechanical Performance of the Alzheimer's Beta Amyloid Fibrils

JOURNAL=Frontiers in Bioengineering and Biotechnology

VOLUME=7

YEAR=2019

URL=https://www.frontiersin.org/journals/bioengineering-and-biotechnology/articles/10.3389/fbioe.2019.00083

DOI=10.3389/fbioe.2019.00083

ISSN=2296-4185

ABSTRACT=<p>Alzheimer's Disease (AD) is related with the abnormal aggregation of amyloid β-peptides Aβ<sub>1−40</sub> and Aβ<sub>1−42</sub>, the latter having a polymorphic character which gives rise to U- or S-shaped fibrils. Elucidating the role played by the nanoscale-material architecture on the amyloid fibril stability is a crucial breakthrough to better understand the pathological nature of amyloid structures and to support the rational design of bio-inspired materials. The computational study here presented highlights the superior mechanical behavior of the S-architecture, characterized by a Young's modulus markedly higher than the U-shaped architecture. The S-architecture showed a higher mechanical resistance to the enforced deformation along the fibril axis, consequence of a better interchain hydrogen bonds' distribution. In conclusion, this study, focusing the attention on the pivotal multiscale relationship between molecular phenomena and material properties, suggests the S-shaped Aβ<sub>1−42</sub> species as a target of election in computational screen/design/optimization of effective aggregation modulators.</p>