Effect of Charge Patterning and Polymer Architecture on Polypeptide-Based Coacervates

Complex coacervation is an electrostatically-driven liquid-liquid phase separation that occurs when aqueous solutions of oppositely-charged polyelectrolytes are mixed. The resultant dense, polymer-rich coacervate phase has been utilized in a variety of different applications, including encapsulation such as gene and drug delivery. Furthermore, direct analogies have been drawn between biomolecule containing coacervate materials and aspects of the intracellular environment. Complex coacervation can be controlled by many factors such as the polycation/polyanion ratio, pH, temperature, architecture, and pattern of charges present. Among these factors, the effect of polymer architecture and charge patterning has been rarely studied due to limitations related to the synthesis of well-controlled polymers with defined branching and/or charge-patterned geometries. Here, we use polypeptides as a model polymer system to examine the effects of both polymer architecture and patterns of matched and mismatched sequences of charged residues on complex coacervation. Additionally, we also examine the effects of incorporating zwitterionic moieties, containing both positive and negative charges in close proximity, as copolymers into our polymers. These experimental efforts are supported by the parallel development of computational approaches for modeling and predicting the phase behavior of patterned polymeric materials. This systematic investigation of the effects of architecture and charge patterning will help to elucidate design rules to facilitate the tailored creation of complex coacervate-based materials with defined properties for a wide range of applications.