Non-Fickian Molecular Transport in Protein–DNA Droplets

Bulk-level measurements of dynamics have suggested that phase-separated, protein-nucleic acid rich droplets can be viewed as simple liquids. In this report, we show that histone proteins spontaneously phase separate into liquid-like droplets in the presence of DNA. Using super-resolution fluorescence microscopy, we find that molecular transport in these droplets is non-Fickian (subdiffusive) at nanoscopic length scales. This observation cannot be explained by charge-charge interactions. Instead, our results strongly suggest that cation-π interactions drive the non-Fickian behavior. Given the ubiquity of cationic and aromatic moieties in protein-nucleic acid rich liquid-like phases observed in cells, we anticipate that non-Fickian diffusion is a general transport mechanism in such phases.