Role of Solvent Compatibility in the Phase Behavior of Binary Solutions of Weakly Associating Multivalent Polymers

Abstract

Condensate formation of biopolymer solutions, prominently those of various intrinsically disordered proteins (IDPs), is determined by 'sticky' interactions between associating residues, multivalently present along the polymer backbone. Using a ternary mean field 'stickers-and-spacers' model, we demonstrate that if sticker association is of the order of a few times the thermal energy, a delicate balance between specific binding and non-specific polymer-solvent interactions gives rise to a particularly rich ternary phase behavior under physiological circumstances. For a generic system represented by a solution comprising multi-associative scaffold and client polymers, the difference in solvent compatibility between the polymers modulates the nature of isothermal liquid-liquid phase separation (LLPS) between associative and segregative. The calculations reveal regimes of dualistic phase behavior, where both types of LLPS occur within the same phase diagram, either associated with the presence of multiple miscibility gaps, or a flip in the slope of the tie-lines belonging to a single coexistence region.

Role of Strong Localized vs. Weak Distributed Interactions in Disordered Protein Phase Separation

“…Strong monomer attraction would lead to the collapse of the chain, mimicking poor solvent conditions, whereas pure repulsion would lead to chain expansion analogous to good solvent conditions. 9,43 Single-chain compactness has been shown to correlate with the propensity to phase separate both experimentally and computationally for a wide range of IDPs. 44–46 Here, we quantified single-chain compactness using the polymer’s radius of gyration R g , which we computed from the average of the trace of the gyration tensor.…”