Atomistic simulation of nanomechanical properties of Alzheimer’s Aβ(1–40) amyloid fibrils under compressive and tensile loading

Abstract In addition to being associated with severe degenerative diseases, amyloids show exceptional mechanical properties including great strength, sturdiness and elasticity. However, thus far physical models that explain these properties remain elusive, and our understanding of molecular deformation and failure mechanisms of individual amyloid fibrils is limited. Here we report a series of molecular dynamics simulations, carried out to analyze the mechanical response of two-fold symmetric Aβ(1–40) amyloid fibrils, twisted protein nanofilaments consisting of a H-bonded layered structure. We find a correlation of the mechanical behavior with chemical and nanostructural rearrangements of the fibril during compressive and tensile deformation, showing that the density of H-bonds varies linearly with the measured strain. Further, we find that both compressive and tensile deformation is coupled with torsional deformation, which is manifested in a strong variation of the interlayer twist angle that is found to be proportional to both the applied stress and measured strain. In both compression and tension we observe an increase of the Young's modulus from 2.34 GPa (for less than 0.1% strain in compression and 0.2% strain in tension), to 12.43 GPa for compression and 18.05 GPa for tension. The moduli at larger deformation are in good agreement with experimental data, where values in the range of 10–20 GPa have been reported. Our studies confirm that amyloids feature a very high stiffness, and elucidate the importance of the chemical and structural rearrangements of the fibrils during deformation.