Metastability of Biological Matter in Liquid Phase Separation

Membraneless organelles (MLOs) form via liquid-liquid phase separation (LLPS). The liquid-like MLOs afford multifold peculiarities including high dynamics, reversibility and responsiveness. The MLOs are typically metastable with a tendency to undergo fast, drastic and reversible formation and dissolution, as well as transition into more stable glassy or gel-like states. Moreover, the alteration of metastability of LLPS is linked with cellular pathology. Here, we review the crucial and ubiquitous ‘metastability’ of MLOs driven by liquid phase separation, from multifaceted regards including energy state, molecular interactions, molecular structure, materials state, as well as the associations with diseases. This review can help to advance the insight into properties and pathogenesis associated with LLPS of biological matter.