Subcompartmentalization of polyampholyte species in organelle-like condensates is promoted by charge pattern mismatch and strong excluded-volume interaction

TL;DR

This study uses polymer field theory and molecular dynamics to show that charge pattern mismatch and excluded volume effects promote the separation of different IDP species in condensates, aiding organelle subcompartmentalization.

Contribution

It reveals how charge pattern mismatch and excluded volume interactions work together to drive subcompartmentalization in phase-separated organelles.

Findings

Charge pattern mismatch promotes demixing of IDPs.

Excluded volume effects enhance phase separation.

Subcompartmentalization may facilitate organelle function.

Abstract

Polyampholyte field theory and explicit-chain molecular dynamics models of sequence-specific phase separation of a system with two intrinsically disordered protein (IDP) species indicate consistently that a substantial polymer excluded volume and a significant mismatch of the IDP sequence charge patterns can act in concert, but not in isolation, to demix the two IDP species upon condensation. This finding reveals an energetic-geometric interplay in a stochastic, "fuzzy" molecular recognition mechanism that may facilitate subcompartmentalization of membraneless organelles.