Molecular dynamics simulations of mechanical failure in polymorphic arrangements of amyloid fibrils containing structural defects

Abstract

We examine how the different steric packing arrangements found in amyloid fibril polymorphs can modulate their mechanical properties using steered molecular dynamics simulations. Our calculations demonstrate that for fibrils containing structural defects, their ability to resist force in a particular direction can be dominated by both the number and molecular details of the defects that are present. The simulations thereby suggest a hierarchy of factors that govern the mechanical resilience of fibrils, and illustrate the general principles that must be considered when quantifying the mechanical properties of amyloid fibres containing defects.

Keywords

• amyloid
• fibril fragmentation
• steered molecular dynamics (SMD)
• structural defects