Designing Coacervate-forming Systems Using Charge Sequence

Oppositely-charged polyelectrolytes can associatively phase separate in a salt solution via a process known as ‘complex coacervation’. Coacervation is driven in part by a large entropic gain due to counterion condensation and release. This drives coacervation by replacing condensed counterions with the oppositely-charged polyelectrolyte, leading to a significant increase in the counterion translational entropy. The magnitude of this entropy change can be tuned by altering the sequence of charged and neutral monomers, which leads to significant changes in phase behavior. We have developed a theoretical model to understand this connection between sequence and phase behavior by mapping the coacervate molecular structure to a 1D adsorption model that can be evaluated using the transfer matrix method. This transfer matrix theory uses inputs from Monte Carlo simulations to determine the phase separation and is able to determine the phase separation of sequence-defined polyelectrolytes. Theoretical results exhibit qualitative agreement with experimental and simulation results. These sequenced systems provide insights into the phase separation of intrinsically-disordered proteins and provides a method to use sequence specificity to tune the phase behavior of coacervate-based materials.