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

Abstract

Amyloid 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.

Mapping the Broad Structural and Mechanical Properties of Amyloid Fibrils

“…S11, E and F, for a comparison of the model and experimentally measured fibril dimensions). Such effects have been described previously (26,47). It has been shown that a gradual increase in the number of monomers in a fibril FIGURE 5 Ashby plot summarizing this study.…”

“…Of interest here is the use of AFM to determine the mechanical properties of amyloid fibrils such as persistence length (1,2,4,23), Young's (elastic) modulus (1,5,24), and strength (25). Constant-velocity steered molecular dynamics (SMD) simulations have also been used effectively to calculate the rupture force in tensile deformation simulations, allowing for estimation of the ultimate strength and Young's (elastic) modulus of amyloid fibrils (26)(27)(28).…”

Measurement of intrinsic properties of amyloid fibrils by the peak force QNM method

“…On the other hand, estimations of Young's moduli of amyloid fibrils by simulations point at numbers in the same order of magnitude as experimental values, yet, systematically higher. [18][19][20][21] Recently, we have reported that peak force quantitative nanomechanical (PF-QNM) AFM shows great potential to be applied as a high-resolution technique to identify structural features and associated nanomechanical properties of amyloid fibrils. 22 Here we further demonstrate that the technique is insensitive to the structural details of the amyloid fibril cross-section, that is to say that the intrinsic stiffness expressed by Young's modulus can be correctly de-coupled from the overall rigidity, to which both Young's modulus and cross-section contribute.…”

Nanomechanics and intermolecular forces of amyloid revealed by four-dimensional electron microscopy

“…The biological implication of this model is that extremely short fibrils are flexible and ductile whereas longer fibrils are stiff and brittle (38) [if we assume, as experiment suggests (39), that fibril fracture occurs through the breakage of longitudinal hydrogen bonds]. Higher rupture forces would be required to fragment low aspect ratio fibrils, because they can deform through shear, whereas longer, high aspect ratio fibrils would become increasingly fractureprone due to the L −2 scaling of critical buckling force for an Euler-Bernoulli beam (36).…”