Anfinsen's dogma emerged from experiments which show that a protein's native 3D folded architecture is encoded within its primary sequence. This insight emerged before almost 40% of eukaryotic proteins were found to contain intrinsically disordered domains with binding partners that are able to template multiple structures and functional outputs. Despite the challenges associated with characterizing such intrinsically disordered protein domains and their interactions with various binding partners, the need to understand how they propagate and regulate context-dependent information now becomes increasingly important. In addition to understanding the complex signaling networks of multicellular organisms, harness their potential will expand the next generation of functional materials. Accordingly, we review progress with model peptides to reveal the rules necessary for precise spatiotemporal assembly of polypeptide materials.

The Central Dogma highlights the mutualistic functions of protein and nucleic acid biopolymers, and this synergy appears prominently in the membraneless organelles widely distributed throughout prokaryotic and eukaryotic organisms alike. Ribonucleoprotein granules (RNPs), which are complex coacervates of RNA with proteins, are a prime example of these membranelles organelles and underly multiple essential cellular functions. Inspired by the highly dynamic character of these organelles and the recent studies that ATP both inhibits and templates phase separation of the fused in sarcoma (FUS) protein implicated in several neurodegenerative diseases, we explored the RNA templated ordering of a single motif of the Aβ peptide of Alzheimer’s disease. We now know that this strong cross-β propensity motif alone assembles through a liquid-like coacervate phase that can be externally templated to form distinct supramolecular assemblies. Now we provide evidence that structured phosphates, ranging from complex structures like double stranded and quadraplex DNA to simple trimetaphosphate, differentially impact the liquid to solid phase transition necessary for paracrystalline assembly. The results from this simple model illustrate the potential of ordered environmental templates in the transition to potentially irreversible pathogenic assemblies and provides insight into the ordering dynamics necessary for creating functional synthetic polymer co-assemblies.