UC Santa Barbara

Catecholic 3,4-dihydroxyphenyl-l-alanine (Dopa) residues in mussel foot proteins (mfps) contribute critically to mussel (Mytilus californianus) plaque adhesion, but only if protected from oxidation at the adhesive-substratum interface. Dopa oxidation is thermodynamically favorable in seawater yet barely detectable in plaques; therefore, we investigated how plaques insulate Dopa-containing mfps against oxidation. Seawater sulfate triggers an mfp3 and mfp6 liquid-liquid phase separation (LLPS). By combining plaque cyclic voltammetry with electrophoresis, mass spectrometry, and redox-exchange chemistry, we show that Dopa-containing mfp3 and mfp6 in phase-separated droplets remain stable despite rapid oxidation in the surrounding equilibrium solution. The results suggest that a cohort of oxidation-prone proteins is endowed with phase-dependent redox stability. Moreover, in forming LLPS compartments, Dopa proteins become reservoirs of chemical energy.