Liquid-liquid phase separation (LLPS) of intrinsically disordered proteins (IDPs) can lead to formation of membrane-less organelles within cells, impacting a variety of biological processes including cell signaling and gene regulation networks. IDPs that demonstrate LLPS often present low-complexity regions containing low amino acid diversity. Leveraging the benefits of consensus protein design, a minimal repeat peptide (Gal) from an IDP, Galactein 3, has been extracted by sequence alignment and polymerized linearly to reconstruct the phase behavior of the parent protein material. As the synthetic, linear IDP with consensus repeats showed selective coacervation with carbohydrates over other biomolecules as the native protein, we are interested in expanding the design space and understanding how the topology of the polypeptides affects the formation of coacervates and the properties of the resulting materials. Here, we prepare a cysteine-contained Gal polypeptide via recombinant protein expression and attach the polypeptide to various short maleimide-functionalized polyethylene glycol linkers in preparation of a series of poly(Gal) with linear, segmented, star-shaped, and bottlebrush architectures. We hypothesize that varying the number of peptide repeats and the chain flexibility in different topologies will affect the strength of interaction with biomolecules, selectivity, and the dynamic of the coacervation. Taken together, we envision that this work will help understand the driving force of coacervate formation and guide the design of IDP-based biomaterials.
