Fig. 1: Condensate ageing process.

a Schematic representation of the accumulation of inter-protein β-sheets within a bulk condensate simulation. The zoomed images depict the nature of the initially intrinsically disordered protein regions (left) and the cross-β-sheet structures formed over time (right). b TDP-43 LCD and FUS LCD sequence representation, highlighting the charged and aromatic residues, as well as the low-complexity aromatic-rich kinked segments (LARKS) as indicated in the legend. c Storage (G') and shear loss (G") moduli as a function of frequency (ω) for non-aged (top) and aged (bottom) FUS LCD condensates. d Time-evolution of cross-β-sheet concentration for FUS LCD and TDP-43 LCD condensates. The continuous lines depict simulation data while the dashed lines represent fits to the data according to a secondary nucleation dominated mechanism (see Section II C for details on these fits). e Simulation of a FUS LCD condensate in bulk conditions containing small peptides that hinder the nucleation of cross-β-sheet structures.