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  • Review Article
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Fluid protein condensates for bio-inspired applications

Nature Reviews Bioengineering volume 2, pages 260–278 (2024)Cite this article

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Abstract

Since the discovery of tropoelastin liquid–liquid phase separation in the 1950s, it has been recognized that fluid protein condensates, including coacervates and liquid crystals, are involved in the biofabrication of functional materials in numerous organisms. Prominent examples include elastin, spider silk, the mussel byssus and various biomineralized tissues as well as less studied systems such as velvet worm slime, sandcastle worm cement and the squid beak; similar mechanisms might lead to amyloid formation in neurodegenerative diseases. Engineers have exploited these fundamental insights to produce synthetic condensates for various biomedical applications. In this Review, we highlight biological systems in which protein condensates are involved in the production of biopolymeric and biocomposite materials (and possible implications of disruption of these structures in pathologies), and we discuss examples where extracted biological concepts have inspired translational applications. We emphasize the common strategies observed between different biological systems for the use of condensates in the assembly of various fibres, adhesives and composites. Finally, we discuss the applications of bio-inspired condensates in drug delivery, biomedical adhesives, tissue engineering and bioengineered composites.

Key points

  • Biocondensates, also called coacervates, form by liquid–liquid phase separation or liquid–liquid crystalline phase separation depending on the rigidity of the biomacromolecules involved.

  • Protein condensates, including coacervates and liquid crystals, are crucial for the assembly of biological fibres, including elastic fibres, amyloid fibrils, spider silk and the mussel byssus core, with extractable concepts for bio-inspired materials.

  • Prominent biological glues from mussels and sandcastle worms leverage characteristic features of protein condensates to achieve remarkable wet adhesion in salty marine environments, providing inspiration for synthetic adhesives.

  • Fluid condensate phases are precursors in the assembly of numerous tough biological composite materials, including squid beaks, hard, flexible coatings produced by mussels and various mineralized tissues.

  • Biocondensates are useful as transient phases during the assembly of biological materials owing to their biophysical characteristics, namely liquid-like properties enabling flow, as well as stimuli-responsive protein precursors and triggered fluid-to-solid transition.

  • Bio-inspired condensates have demonstrated promising potential for biomedical applications, including as safe drug-delivery systems, bio-adhesives for soft and hard tissue repair and scaffolds for tissue engineering.

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Fig. 1: Properties of phase separation processes.
Fig. 2: Formation of fibres from biomolecular fluid protein condensates.
Fig. 3: Formation of adhesives from biomolecular fluid protein condensates.
Fig. 4: Formation of biocomposites from biomolecular fluid protein condensates.
Fig. 5: Bio-inspired applications of biocondensates.

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Acknowledgements

M.J.H. acknowledges financial support from a Canada Research Chair Award (CRC Tier 2 950-231953). A.M. acknowledges financial support from the Singapore Ministry of Education (MOE) through an Academic Research (AcRF) Tier 3 grant (No. MOE 2019-T3-1-012) and from the strategic initiative on biomimetic and sustainable materials at Nanyang Technological University.

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Authors and Affiliations

  1. Department of Chemistry, McGill University, Montreal, Quebec, Canada

    Matthew J. Harrington

  2. Department of Health Sciences and Technology, ETH Zurich, Zurich, Switzerland

    Raffaele Mezzenga

  3. Department of Materials, ETH Zurich, Zurich, Switzerland

    Raffaele Mezzenga

  4. Biological and Biomimetic Material Laboratory, Center for Sustainable Materials, School of Materials Science and Engineering, Nanyang Technological University, Singapore, Singapore

    Ali Miserez

  5. School of Biological Sciences, Nanyang Technological University, Singapore, Singapore

    Ali Miserez

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Harrington, M.J., Mezzenga, R. & Miserez, A. Fluid protein condensates for bio-inspired applications. Nat Rev Bioeng 2, 260–278 (2024). https://doi.org/10.1038/s44222-023-00133-6

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