Dissecting the structural determinants for the difference in mechanical stability of silk and amyloid beta-sheet stacks

Stacking of beta-sheets results in a protein super secondary structure with remarkable mechanical properties. beta-Stacks are the determinants of a silk fiber's resilience and are also the building blocks of amyloid fibrils. While both silk and amyloid-type crystals are known to feature a high resistance against rupture, their structural and mechanical similarities and particularities are yet to be fully understood. Here, we systematically compare the rupture force and stiffness of amyloid and spider silk poly-alanine beta-stacks of comparable sizes using Molecular Dynamics simulations. We identify the direction of force application as the primary determinant of the rupture strength; beta-sheets in silk are orientated along the fiber axis, i.e. the pulling direction, and consequently require high forces in the several nanoNewton range for shearing beta-strands apart, while beta-sheets in amyloid are oriented vertically to the fiber, allowing a zipper-like rupture at sub-nanoNewton forces. A secondary factor rendering amyloid beta-stacks softer and weaker than their spider silk counterparts is the sub-optimal side-chain packing between beta-sheets due to the sequence variations of amyloid-forming proteins as opposed to the perfectly packed poly-alanine beta-sheets of silk. Taken together, amyloid fibers can reach the stiffness of silk fibers in spite of their softer and weaker beta-sheet arrangement as they are missing a softening amorphous matrix.