Liquid‐Like Phases Preorder Peptides for Supramolecular Assembly

Abstract

Controlling supramolecular assembly remains a major challenge for materials science and synthetic biology. Biopolymers organize into multimolecular architectures via two‐step nucleation processes involving dynamic intermediate solute‐rich phases. Here we present spectroscopic analyses of metastable phases formed with a congener of the Alzheimer's disease Aβ peptide that reveals diverse populations of single β‐sheets. The degree of order in this liquid‐like particle phase is remarkable both in the range of sheets and the selection of a single propagating nucleus. The resulting fibril seed is less stable in solution and cooperatively transforms into another fibril. The conformational dynamics of this peptide provide a mechanistic model for controlling the range of polymorphic amyloid assemblies in health and disease.