Chemically active droplets in crowded environments

TL;DR

This paper explores how macromolecular crowding influences chemically active biomolecular condensates, revealing that crowding reduces droplet size but increases dense phase volume through complex nonequilibrium interactions.

Contribution

It combines particle-based and field-based models to quantitatively analyze the effects of crowding on chemically active droplets in cellular environments, highlighting nonintuitive behaviors.

Findings

Crowding reduces droplet size

Crowding expands dense phase volume

Depletion interactions and diffusion hinderance are key factors

Abstract

Biomolecular condensates are essential for cellular organization and result from phase separation in systems far from thermodynamic equilibrium. Among various models, chemically active droplets play a significant role, consisting of proteins that switch between attractive and repulsive states via nonequilibrium chemical reactions. While field-based simulations have provided insights into their behavior, these coarse-grained approaches fail to capture molecular-scale effects, particularly in crowded cellular environments. Macromolecular crowding, a key feature of intracellular organization, strongly influences molecular transport within condensates, yet its quantitative impact remains underexplored. This study investigates the interplay between chemically active droplets and crowders by using particle-based models, that provide molecular insight, and a field-based model, that complements this picture. Surprisingly, crowding reduces droplet size while expanding the overall dense phase volume, challenging equilibrium-based expectations. This effect arises from the interplay between depletion interactions, diffusion hindrance, and nonequilibrium particle fluxes. Our findings provide a step towards a more comprehensive understanding of chemically active droplets in complex, realistic cellular environments.