Figure 1.

The fiber self-assembly pathway. (A) Fiber formation from building block 1. Upon oxidation (1) the monomer forms a mixture of macrocycles that can interchange building blocks with one another through disulfide exchange reactions (2). Following slow nucleation (3), 1₆ can elongate by the stacking of additional hexamer macrocycles (4). (B) Representative kinetic analysis of relative molecular concentrations over time, performed using ultra-performance-liquid-chromatography (UPLC) under stirred conditions. Concentration of monomer (1) (■) diminishes by reaction with oxygen to form small, soluble macrocycles (cyan ▲). After an initial lag phase (roughly 500 min), the concentration of hexamer (1₆) (orange ●) increases as fibers are formed. Insets show the coarse-grained models of monomer, trimer (1₃), tetramer (1₄), and stacks of hexamers (fibers), and a high-resolution AFM image of a single fiber on a lipid bilayer (top right, scale bar 10 nm). Amino acid side chains are not shown in the coarse-grained models. (C) Model representation of the self-assembly pathway summarizing the main findings of the present work (see main text).