Liquid-liquid phase separation: Fundamental physical principles, biological implications, and applications in supramolecular materials engineering

Liquid-liquid phase separation (LLPS) is a captivating phenomenon in which a uniform mixture spontaneously divides into two liquid phases with differing component concentrations. It is prevalent in soft matter, is observed in systems involving polymers, organic molecules, and proteins, and is influenced by environmental factors and component properties. Recent recognition of LLPS within living organisms reveals its role in creating cellular compartments to orchestrate complex biochemical reactions, requiring distinct boundaries and unhindered molecular movement. Nonmembrane compartments, stemming from cytoplasmic LLPS, such as nucleoli, hold promise for synthetic cell engineering and cellular function insights. Under certain conditions, LLPS is linked to diseases such as sickle-cell disease, cancer, and neurodegenerative diseases. This review offers a concise overview of LLPS in soft matter, emphasizing its relevance in soft material engineering. We delve into fundamental mechanisms, focusing on biological systems, and explore the implications of LLPS, spanning organelles, substance exchange, molecular diffusion, and disease associations. LLPS enables soft material engineering, with applications in biomedicine and bioengineering, shaping future possibilities in bioengineering, from foundational cellular constructs to intricate artificial tissue development.