Rheostatic Network Consolidation Drives Physical Aging in Biomolecular Condensates
Polanco, D.; Pele, K. G.; Mairo, A.; Martinez-Monge, M.; Moreno, N.; Cremades, N.
Show abstract
While the physical aging of biomolecular condensates into macroscopic glasses is heavily linked to pathological disease states, the nanoscale topological rules governing this non-equilibrium relaxation remain elusive. Using heterotypic alpha-synuclein-Tau coacervates, we combine variable-stringency dissolution and FLIM-FRET to provide direct experimental mapping of the internal network reorganization over time. Rather than a passive, isotropic kinetic jamming event typical of classic glasses, we demonstrate that this physical aging is driven by continuous rheostatic network consolidation; a progressive, directed topological relaxation toward deeper free-energy minima powered by the cooperative spatial optimization of sticker motifs. We formalize these dynamics into a mesoscale series-resistance model derived from size-resolved kinetics, proving that thermodynamic quench depth dictates the initial network state while clustered sticker patterning introduces configurational frustration that kinetically stalls maturation to preserve liquidity. This multi-scale framework links sequence grammar to non-equilibrium transport laws, revealing how biomolecular assemblies navigate the boundary between physiological utility and pathological arrest.
Matching journals
The top 5 journals account for 50% of the predicted probability mass.