Hydrogen-bonds mediate liquid-liquid phase separation of mussel derived adhesive peptides

Marine mussels achieve strong underwater adhesion by depositing mussel foot proteins (Mfps) that form coacervates during the protein secretion. However, the molecular mechanisms that govern the phase separation behaviors of the Mfps are still not fully understood. Here, we report that GK-16*, a peptide derived from the primary adhesive protein Mfp-5, forms coacervate in seawater conditions. Molecular dynamics simulations combined with point mutation experiments demonstrate that Dopa- and Gly-mediated hydrogen-bonding interactions are essential in the coacervation process. The properties of GK-16* coacervates could be controlled by tuning the strength of the electrostatic and Dopa-mediated hydrogen bond interactions via controlling the pH and salt concentration of the solution. The GK-16* coacervate undergoes a pH induced liquid-to-gel transition, which can be utilized for the underwater delivery and curing of the adhesives. Our study provides useful molecular design principles for the development of mussel-inspired peptidyl coacervate adhesives with tunable properties.

Automated summary

This study reveals that a peptide derived from mussel adhesive protein can form coacervates in seawater conditions. The hydrogen bonding interactions mediated by dopamine and glycine are important for the coacervation process. The properties of the coacervates can be controlled by adjusting the pH and salt concentration of the solution, and the coacervate undergoes a liquid-to-gel transition induced by pH change, which can be used for underwater adhesive applications.