Mechanical and thermodynamic properties of Aβ₄₂ , Aβ₄₀ and α-synuclein fibrils from molecular-scale simulation

Atomic force microscopy (AFM) is a versatile tool to characterise the mechanical properties of biological systems. However, AFM deformations are tiny, which makes impossible the analysis of the mechanical response by experiment. Here, we have employed a simulation protocol to determine the elastic properties of several biopolymers (i.e. biological fibrils) . For these systems, the simulation approach is sufficient to provide reliable values for three different types of elastic deformation, i.e. tensile (Y_L), shear (S), and indentation (Y_T). Our results enable the comparison of the mechanical properties of these fibrils. In particular, we find a significant elastic anisotropy between axial and transverse directions for all systems. In addition, our methodology is sensitive to molecular packing of the fibrils . Interestingly, our results suggest a significant correlation between mechanical stability and aggregation propensity (rate) in amyloid systems, that is, the higher the mechanical stability the faster the fibril formation takes place.