Sequence-specific polyampholyte phase separation in membraneless organelles

TL;DR

This paper develops a theoretical framework using the random phase approximation to understand electrostatic effects in polyampholyte phase separation, providing insights into the sequence dependence of IDP-driven membraneless organelles.

Contribution

It introduces a general analytical theory for charge pattern effects on IDP phase separation, validated against experimental data.

Findings

Theory aligns with experimental observations of Ddx4

Predicts sequence-dependent phase behavior

Applicable to various charge patterns

Abstract

Liquid-liquid phase separation of charge/aromatic-enriched intrinsically disordered proteins (IDPs) is critical in the biological function of membraneless organelles. Much of the physics of this recent discovery remains to be elucidated. Here we present a theory in the random phase approximation to account for electrostatic effects in polyampholyte phase separations, yielding predictions consistent with recent experiments on the IDP Ddx4. The theory is applicable to any charge pattern and thus provides a general analytical framework for studying sequence dependence of IDP phase separation.