John H. Dillon Medal (2024): Developing Straightforward Models to Address Complex (Coacervate) Problems in Sequence-Defined Polyelectrolytes*

Polyelectrolytes have been studied for decades, however understanding their physical properties remains a persistent challenge in polymer physics. The importance of charged polymers has only become more apparent with time, due to their widespread use in applications ranging from food additives to paints, and their relevance in biological systems. Indeed, it is the biological world that shows just how promising polyelectrolytes are as materials; the building blocks of life such as proteins, DNA, RNA, and polysaccharides all rely on charge for their function and structure. Recently, there has been significant interest in understanding biomolecular condensates, intracellular structures that are known to form from many of these charged biomacromolecules. These condensates are formed by a liquid-liquid phase separation process, and are driven in part by attractive electrostatic interactions. One intriguing feature of these condensates is their sensitivity to the charged monomer 'sequence' of participating disordered proteins. 

Inspired by the role of sequence in these biophysical systems, we studied an analogous class of polyelectrolyte materials known as complex coacervates, which are aqueous solutions of oppositely-charged macromolecules and salt that exhibit associative phase separation. We pursue an integrated computational and theoretical study, in collaboration with experimentalists, to demonstrate that coacervates are highly sensitive to the precise patterning of charges and other chemical and physical aspects of their environment. We elucidate the key molecular features that play a large role in coacervate thermodynamics. Building upon these insights, we demonstrate how coacervate phase behavior and assembly can be strongly tuned via specific charge sequences. Ultimately, our goal is to establish molecular-level design rules to facilitate the tailored creation of materials based on complex coacervation that can both illuminate self-assembly phenomena found in nature, and find utility across a wide range of real-world applications.