Electrostatic Depletion Force in Complex Coacervates

TL;DR

This paper reveals electrostatic depletion as a universal force driving guest macromolecule aggregation in complex coacervates, fundamentally altering understanding of their molecular interactions and aiding design of biomedical applications.

Contribution

It introduces electrostatic depletion as a novel, dominant aggregation mechanism in coacervates, supported by extensive MD simulations, contrasting traditional depletion effects.

Findings

Electrostatic depletion causes effective attraction of neutral and low-charge polymers.

Guest aggregation occurs even without chemical incompatibility.

Electrostatic depletion differs from traditional depletion by involving similarly sized polymers.

Abstract

The functionalities and applications of complex coacervates -- liquid condensates resulting from liquid-liquid phase separation of charged polymers -- are significantly influenced by the dispersion and aggregation states of guest macromolecules. Intriguingly, guest macromolecules exhibit a strong tendency to aggregate within coacervates even in the absence of apparent chemical incompatibility, indicating a universal aggregation mechanism at play in these environments. Using extensive MD simulations, we identify electrostatic depletion -- a strong force arising from electrostatic correlations within the host polyelectrolyte network that drives guest aggregations. Due to electrostatic depletion, neutral polymers, low-charge-density polyelectrolytes, and intrinsically disordered proteins (IDPs) exhibit effective attractions in coacervates, in stark contrast to their behavior in dilute solutions. Unlike traditional depletion effect that requires mismatched length scale and morphology, electrostatic depletion is relevant in fluid systems where solute and solvent are both polymers with comparable size. Our discovery bridges a critical knowledge gap in the molecular physics of densely charged, crowded liquids and holds significant implications for the design of synthetic protocells and advanced drug delivery systems.