Heterochromatin Protein HP1 Gelation Dynamics Revealed by Solid-State NMR Spectroscopy

Heterochromatin protein 1 (HP1) undergoes liquid-liquid phase separation (LLPS) and forms liquid droplets and gels invitro, properties that also appear to be central to its biological function in heterochromatin compaction and regulation. Here we use solid-state NMR spectroscopy to track the conformational dynamics of phosphorylated HP1 during its transformation from the liquid to the gel state. Using experiments designed to probe distinct dynamic modes, we identify regions with varying mobilities within HP1 molecules and show that specific serine residues uniquely contribute to gel formation. The addition of chromatin disturbs the gelation process while preserving the conformational dynamics within individual bulk HP1 molecules. Our study provides a glimpse into the dynamic architecture of dense HP1 phases and showcases the potential of solid-state NMR to detect an elusive biophysical regime of phase separating biomolecules.