“Nature or nurture” – How environmental factors influence the conformational memory of amyloid fibrils

Abstract

Amyloid fibrils are complex protein structures with multilayered chiral architecture, that are known to self-propagate. The replication of the mother seed structure by daughter fibrils is known as conformational or templated memory. Using vibrational circular dichroism (VCD), electronic circular dichroism (ECD), transmission electron microscopy (TEM), and cryo-electron microscopy (cryo-EM) we have shown that environmental factors (here agitation) can be a competing force against the templated growth of human lysozyme fibrils. In the cross-seeding experiment non-agitated daughters preserved the structure of agitated mothers, whereas agitated daughters did not always exhibit the same characteristics as their non-agitated mothers. This pattern was reflected on various levels of fibril architecture (secondary structure, protofilament handedness, morphology), demonstrating that the structural indeterminism originates from deeper levels of the fibril structure. This observation may contribute to a better understanding of the processes behind fibril formation.