Data from: Decoupling phase separation and fibrillization preserves activity of biomolecular condensates

Age-dependent conversion of metastable, liquid-like protein condensates
into amyloid fibrils is observed across many protein systems linked to
neurodegeneration. A critical question is whether the thermodynamic forces
governing reversible phase separation can be decoupled from those driving
irreversible amyloid formation. This study addresses this question using
an engineered variant of the microtubule-associated protein Tau that forms
biochemically active condensates. Under quiescent, cofactor-free
conditions, these protein condensates undergo rapid aging into amyloid
fibrils, with the condensate interface serving as a site for fibril
nucleation. This accompanies loss of condensate activity in tubulin
recruitment and microtubule assembly. The small-molecule metabolite
L-arginine selectively suppresses the condensate-to-fibril transition
without disrupting phase separation, acting in a valence- and
chemistry-dependent manner. By increasing condensate viscoelasticity,
L-arginine mitigates age-dependent functional decline of Tau condensates,
demonstrating that small molecules can stabilize condensate metastability
and preserve function.