Entropic Clustering of Stickers Induces Aging in Biocondensates

TL;DR

This paper models biomolecular condensates as networks of stickers and spacers, revealing how entropy-driven interactions induce slow aging and glassy dynamics, thus explaining the transition from liquid to solid states.

Contribution

It introduces a minimal model linking microscopic sticker-spacer interactions to macroscopic aging and glassy relaxation in condensates, emphasizing entropy effects.

Findings

Entropy maximization causes attractive forces between stickers.

The model exhibits slow relaxation similar to glassy systems.

Clustering dynamics explain the origin of aging in condensates.

Abstract

Biomolecular condensates are cellular phase-separated droplets that 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. Condensates usually exhibit a solidification over a long period of time (days), a phenomenon described as aging.The emergence of such a long timescale of evolution from microscopic processes, 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 maximization 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.