A Lattice Model of Charge-Pattern-Dependent Polyampholyte Phase Separation

TL;DR

This study models how charge sequence patterns in polyampholytes influence their phase separation behavior, using lattice-based simulations and theoretical analysis to reveal sequence-dependent critical temperatures and phase behaviors.

Contribution

It introduces a lattice-based heteropolymer model to study sequence-dependent phase separation, providing insights into charge pattern effects on LLPS of IDPs.

Findings

Sequence charge pattern significantly affects phase separation propensity.

Blocky charge sequences have higher critical temperatures for phase separation.

Simulation results align qualitatively with RPA theory but show milder sequence dependence.

Abstract

In view of recent intense experimental and theoretical interests in the biophysics of liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs), heteropolymer models with chain molecules configured as self-avoiding walks on the simple cubic lattice are constructed to study how phase behaviors depend on the sequence of monomers along the chains. To address pertinent general principles, we focus primarily on two fully charged 50-monomer sequences with significantly different charge patterns. Each monomer in our models occupies a single lattice site and all monomers interact via a screened pairwise Coulomb potential. Phase diagrams are obtained by extensive Monte Carlo sampling performed at multiple temperatures on ensembles of 300 chains in boxes of sizes ranging from $52\times 52\times 52$ to $246\times 246\times 246$ to simulate a large number of different systems with the overall polymer volume fraction $\phi$ in each system varying from $0.001$ to $0.1$. Phase separation in the model systems is characterized by the emergence of a large cluster connected by inter-monomer nearest-neighbor lattice contacts and by large fluctuations in local polymer density. The simulated critical temperatures, $T_{\rm cr}$, of phase separation for the two sequences differ significantly, whereby the sequence with a more "blocky" charge pattern exhibits a substantially higher propensity to phase separate. The trend is consistent with our sequence-specific random-phase-approximation (RPA) polymer theory, but the variation of the simulated $T_{\rm cr}$ with a previously proposed "sequence charge decoration" pattern parameter is milder than that predicted by RPA. Ramifications of our findings for the development of analytical theory and simulation protocols of IDP LLPS are discussed.