Phase separation and ageing of glycine-rich protein from tick adhesive

Abstract

Hard ticks feed on their host for multiple days. To ensure firm attachment, they secrete a protein-rich saliva that eventually forms a solid cement cone. The underlying mechanism of this liquid-to-solid transition is currently not understood. This study focuses on the phase transitions of a disordered glycine-rich protein (GRP) found in tick saliva. We show that GRP undergoes liquid–liquid phase separation via simple coacervation to form biomolecular condensates in salty environments. Cation–π and π–π interactions mediated by periodically placed arginine and aromatic amino-acid residues are the primary driving forces that promote phase separation. Interestingly, GRP condensates exhibit ageing by undergoing liquid-to-gel transition over time and exhibit adhesive properties, similar to the naturally occurring cement cone. Finally, we provide evidence for protein-rich condensates in natural tick saliva. Our findings provide a starting point to gain further insights into the bioadhesion of ticks, to develop novel tick control strategies, and towards achieving biomedical applications such as tissue sealants. Ticks adhere firmly to their host by secreting a protein-rich saliva that eventually forms a solid bioadhesive, but the mechanism underlying this phase transition is not understood. Now it has been shown that a disordered glycine-rich protein present in tick saliva undergoes liquid–liquid phase separation, followed by a liquid-to-gel transition, and exhibits adhesive properties.