Mesoscopic viscous-to-elastic transition underlies aging of biomolecular condensates

Abstract

Aging of biomolecular condensates, which progressively leads to solid-like states, is closely linked to biological functions and diseases. However, a unified physical picture that captures the aging dynamics remains elusive. Here, we introduce a phenomenological model in which a condensate is a composite of viscous and elastic elements with coexisting serial and parallel connections. The model naturally yields a relaxation modulus with two relaxation times, unifying the Maxwell and Jeffreys models as special limits. When applied to aging PGL-3 condensates, our model reveals that aging is primarily driven by the conversion of viscous elements into elastic ones. In contrast, the mesoscopic structure topology of the condensates remains approximately invariant. Our stochastic theory of element dynamics also predicts that the condensate viscosity either increases exponentially, in agreement with experiments, or as a power law of the waiting time, governed by a single parameter that depends on temperature and the molecular interaction strength.