Engineering the Liquid-to-Solid Transition of Biomolecular Condensates: Molecular Mechanisms, Control Strategies, and Applications.

Biomolecular condensates are formed through liquid-liquid phase separation (LLPS). They are highly dynamic, membraneless compartments within cells. The liquid-to-solid transition (LST) of these condensates plays a central role in regulating cellular physiological functions, maintaining tissue structural stability, and driving disease progression. Engineering LST has emerged as a major research frontier, integrating biophysics, synthetic biology, and materials science. This review systematically outlines the molecular grammar governing LST, key engineering strategies for its spatiotemporal control, and emerging applications in designed biological systems. We further discuss current challenges and future directions for harnessing LST as a design principle in systems chemistry and synthetic biology.