  Mechanical strength of amyloid beta fibrils has been known to be correlated
with neuronal cell death. Here, we resorted to steered molecular dynamics (SMD)
simulations to mechanically stretch a single S-shape amyloid beta Abeta11-42
dodecamer fibril in vacuum. It was found that the weakest sites at which the
fibril was ruptured due to mechanical extension were exclusively at the
interfaces of alanine and glutamic acid distributed throughout the fibril. It
was also revealed that the free energy required to unfold the fibril to form a
long linear conformation is equivalent to ~ 210 eV, being several thousand
times larger than thermal voltage at room temperature. As a consequence, within
solution a larger free energy is needed for such a maximal stretching based on
the fact that amyloid beta fibrils are structurally more stable in solution due
to the interplay between their hydrophobic cores and solution's entropy.
