Amyloid stability and condensate material properties independently govern the hnRNPA2 condensate to fibril transition

The hnRNPA2 low-complexity domain forms a reproducible fibril fold, and an aromatic triad in the fibril core controls fibril formation kinetics and thermodynamic stability.

• Why it matters: Condensate-to-fibril transitions in RNA/protein membraneless organelles are linked to disease, but how amyloid structure shapes this process is not well defined.
• What they did: Using structure-guided thermodynamic profiling, peptide design, mutagenesis, and in vitro characterization in one-phase versus two-phase condensate conditions, they mapped molecular determinants of assembly.
• The result: Condensate stability and fibril stability are largely independent, and microrheology linked reduced condensate viscosity to faster fibril formation, supporting an interplay between a disordered “fuzzy coat” and the aromatic triad.

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