Microscopic model for aging of biocondensates

Abstract

Biomolecular condensates are membraneless compartments in the cell that are involved in a wide diversity of biological processes. These phase-separated droplets usually exhibit a viscoelastic mechanical response. A behavior rationalized by modeling the complex molecules that make up a condensate as stickers and spacers, which assemble into a network-like structure. The proper functioning of biocondensates requires precise control over their composition, size, and mechanical response. For example, several neurodegenerative diseases are associated with dysfunctional condensates that solidify over a long period of time (days) until they become solid. A phenomenon usually described as aging. The emergence of such a long timescale of evolution from microscopic events, as well as the associated microscopic reorganization leading to aging, remains mostly an open question. In this article, we explore the connection between the mechanical properties of the condensates and their microscopic structure. We propose a minimal model for the dynamic of stickers and spacers, and show that entropy minimization of spacers leads to an attractive force between stickers. Our system displays a surprisingly slow relaxation toward equilibrium, reminiscent of glassy systems and consistent with the liquid-to-solid transition observed. To explain this behavior, we study the clustering dynamic of stickers and successfully explain the origin of glassy relaxation.