Failure of Abeta(1-40) amyloid fibrils under tensile loading

Raffaella Paparcone,Markus Buehler

doi:10.1038/npre.2010.5174.1

Raffaella Paparcone, Markus Buehler

Open Access

https://doi.org/10.1038/npre.2010.5174.1

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Abstract

AbstractAmyloid fibrils and plaques are detected in the brain tissue of patients affected by Alzheimer’s disease, but have also been found as part of normal physiological processes such as bacterial adhesion. Due to their highly organized structures, amyloid proteins have also been used for the development of novel nanomaterials, for a variety of applications including biomaterials for tissue engineering, nanolectronics, or optical devices. Past research on amyloid fibrils resulted in advances in identifying their mechanical properties, revealing a remarkable stiffness. However, the failure mechanism under tensile loading has not been elucidated yet, despite its importance for the understanding of key mechanical properties of amyloid fibrils and plaques as well as the growth and aggregation of amyloids into long fibers and plaques. Here we report a molecular level analysis of failure of amyloids under uniaxial tensile loading. Our molecular modeling results demonstrate that amyloid fibrils are extremely stiff with a Young’s modulus in the range of 18-30 GPa, in good agreement with previous experimental and computational findings. The most important contribution of our study is our finding that amyloid fibrils fail at relatively small strains of 2.5% to 4%, and at stress levels in the range of 1.02 to 0.64 GPa, in good agreement with experimental findings. Notably, we find that the strength properties of amyloid fibrils are extremely length dependent, and that longer amyloid fibrils show drastically smaller failure strains and failure stresses. As a result, longer fibrils in excess of hundreds of nanometers to micrometers have a greatly enhanced propensity towards spontaneous fragmentation and failure. We use a combination of simulation results and simple theoretical models to define critical fibril lengths where distinct failure mechanisms dominate.

Highlights

Solely associated with severe disorders [1], amyloid protein materials are recognized as common protein structures with important biological functional roles [1,2,3] as bacterial coatings [1], protective materials in egg envelopes of several fish species and insects [4, 5] and scaffold for catalytic reactions [6]
The analysis reported in this paper has, as a primary objective, the elucidation of molecular failure mechanisms, strength properties and associated characteristic length-scale ranges where the amyloid fibril mechanical response and failure can be distinguished on the basis of its geometry
This paper shows that individual amyloid fibrils are stiff but brittle mechanical elements, and that amyloid fibrils with longer lengths become increasingly weak and brittle

Summary

Introduction

Solely associated with severe disorders [1], amyloid protein materials are recognized as common protein structures with important biological functional roles [1,2,3] as bacterial coatings [1], protective materials in egg envelopes of several fish species and insects [4, 5] and scaffold for catalytic reactions [6]. Amyloid protein materials often result from protein misfolding pathways that generate fibrillar aggregates with a common core structure consisting of an elongated stack of beta-strands stabilized by a dense network of hydrogen bonds [7] This structural arrangement confers high stability and remarkable mechanical properties, which have been investigated both theoretically and experimentally [8,9,10,11]. The exceptional mechanical properties of amyloids make them good candidates for a wide range of potential technological applications, and as new bionanomaterials utilizing them as nanowires [13,14,15,16], gels [17,18,19,20,21], scaffolds and biotemplates [13, 22,23,24,25,26,27], liquid crystals [28], adhesives [29] and biofilm materials [30] These applications often imply the functionalization of the amyloid fibrils with the introduction of additional elements, including enzymes, metal ions, fluorophores, biotin or cytochromes. Amyloids have been proposed for biological applications in cell adhesion [31] and as bioadhesives for tissue regeneration and engineering [32], on the basis that amyloid toxicity is associated with oligomeric species or pre-fibrillar intermediates rather than mature fibrils [33, 34]

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