Mussels Fabricate Porous Glues via Multiphase Liquid–Liquid Phase Separation of Multiprotein Condensates

Research output: Contribution to journalResearch articleContributedpeer-review


  • Max Renner-Rao - (Author)
  • Franziska Jehle - (Author)
  • Tobias Priemel - (Author)
  • Emilie Duthoo - (Author)
  • Peter Fratzl - (Author)
  • Luca Bertinetti - , Chair of Bioprospecting, Max Planck Institute of Colloids and Interfaces (Author)
  • Matthew J. Harrington - (Author)


Mussels (Mytilus edulis) adhere to hard surfaces in intertidal marine habitats with a porous underwater glue called the byssus plaque. The plaque is an established role model for bioinspired underwater glues and comprises at least six proteins, most of which are highly cationic and enriched in the post-translationally modified amino acid 3,4-dihydroxyphenylalanine (DOPA). While much is known about the chemistry of plaque adhesion, less is understood about the natural plaque formation process. Here, we investigated plaque structure and formation using 3D electron microscopic imaging, revealing that micro- and nanopores form spontaneously during secretion of protein-filled secretory vesicles. To better understand this process, we developed a method to purify intact secretory vesicles for in vitro assembly studies. We discovered that each vesicle contains a sulfate-associated fluid condensate consisting of ∼9 histidine- and/or DOPA-rich proteins, which are presumably the required ingredients for building a plaque. Rupturing vesicles under specific buffering conditions relevant for natural assembly led to controlled multiphase liquid-liquid phase separation (LLPS) of different proteins, resulting in formation of a continuous phase with coexisting droplets. Rapid coarsening of the droplet phase was arrested through pH-dependent cross-linking of the continuous phase, producing native-like solid porous "microplaques"with droplet proteins remaining as fluid condensates within the pores. Results indicate that histidine deprotonation and sulfates figure prominently in condensate cross-linking. Distilled concepts suggest that combining phase separation with tunable cross-linking kinetics could be effective for microfabricating hierarchically porous materials via self-assembly.


Original languageEnglish
Pages (from-to)20877-20890
Number of pages14
JournalACS nano
Issue number12
Publication statusPublished - 27 Dec 2022

External IDs

Scopus 85142664784
WOS 000890500000001
Mendeley c4760bb7-6510-32d3-bc38-7bb62ae6d5db


Sustainable Development Goals


  • adhesion, coacervation, liquid-liquid phase separation (LLPS), mussel byssus, protein condensates, self-assembly, Coacervation, Self-assembly, Mussel byssus, Adhesion, Protein condensates