Liquid-liquid phase separation of proteins and peptides derived from biological materials: Discovery, protein engineering, and emerging applications

Biological materials represent a major source of inspiration to engineer protein-based polymers that can replicate the properties of living systems. Combined with our ability to control the molecular structure of proteins at the single amino acid level, this results in a vast array of attractive possibilities for materials science, an interest that is undeniably related to simplified procedures in gene synthesis, cloning, and biotechnological production. In parallel, it has been increasingly appreciated that living organisms exploit liquid-liquid phase separation (LLPS) to fabricate extracellular structures. In this article, we discuss the central role of protein LLPS in the fabrication of selected biological structures, including biological adhesives and hard biomolecular composites, and how physicochemical lessons from these systems are being replicated in synthetic analogs. Recent translational applications of protein LLPS are highlighted, notably aqueous-resistant adhesives, stimuli-responsive therapeutics carriers, and matrix materials for green structural composites.