Sequence-Tunable Phase Behavior and Unexpected Fluorescence in Designed, Dynamically Interacting Peptide Networks

The liquid-liquid demixing of proteinaceous material is sustained by a network of weakly binding interactions among amino acids’ side chains (e.g., electrostatic, cation<i>-</i> and -) and it has been demonstrated that the distribution of such side chains significantly affects their phase separation behavior.<br/>Here, we report <i>de novo</i> engineering of peptide analogues for systematically depicting the impact on the phase behavior of the chemical structure of the amino acids’ moieties and their nonrandom allocation. Uniformly mixed solution, aggregates, or simple coacervates can be obtained tuning the composition and the patterning of repeats of the motif R/HxxxY, in a pH responsive manner.<br/>Moreover, self-coacervating peptides exhibit a sequence-specific intrinsic fluorescence that is readily observable by confocal microscopy, allowing their specific characterization without any additional dye. Displaying a high cell uptake efficiency, these artificial membraless compartments readily cross the cell membrane and can potentially serve as label-free delivery platform for macromolecular therapeutics.