Engineering Protein–Polyelectrolyte Interactions for Cellular Applications

Protein–polyelectrolyte interactions are fundamental interactions in biology that occur at every length scale, from protein–DNA complexes to phase-separated organelles. They drive processes ranging from gene transcription and DNA synthesis to viral assembly. Protein engineering is a powerful way to modulate these interactions, both to probe endogenous function and to engineer novel interactions between species. In this review, we consider the various noncovalent interactions that govern the formation and behavior of these complexes, and we discuss how protein modifications such as changes to structure, charge, and charge patterning affect them. We highlight recent examples where engineering changes to protein–polyelectrolyte interactions have helped elucidate biological function, and we then focus on recent efforts toward de novo material design of synthetic biomolecular condensates and functional nanoassemblies.