Inert polymer crowders drive phase separation of polyampholyte-like proteins by enhancing electrostatic correlation
Phys. Rev. E 114, 035430 – Published 23 September, 2026
DOI: https://doi.org/10.1103/51q6-sl9p
Abstract
Inert polymer crowders ubiquitously promote the liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs), yet the underlying mechanisms remain elusive. By evaluating the potential of mean force between polyampholyte-like IDPs, we demonstrate that the presence of inert polymer crowders induces conformational transitions by screening the excluded-volume interactions of the IDPs, indirectly enhancing interchain electrostatic correlations. Under physiological conditions, this enhanced correlation is sufficient to trigger LLPS of highly charged IDPs that would otherwise remain dispersed. Our work highlights a universal crowder-conformation-electrostatics coupling in driving LLPS.
