Sequence determinants and solution conditions underlying liquid to solid phase transition

Life consists of numberless functional biomolecules that exist in various states. Besides well-dissolved phases, biomolecules especially proteins and nucleic acids can form liquid droplets through liquid-liquid phase separation (LLPS). Stronger interactions promote a solid-like state of biomolecular condensates, which are also formerly referred to as detergent-insoluble aggregates. Solid-like condensates exist in vivo physiologically and pathologically, and their formation has not been fully understood. Recently, more and more research has proven that liquid to solid phase transition (LST) is an essential way to form solid conden-sates. In this review, we summarized the regions in the sequence that have different impacts on phase transition and empha-sized that the LST is affected by its sequence characteristics. Moreover, increasing evidence unveiled that LST is affected by various solution conditions. We discussed solution conditions like protein concentration, pH, ATP, ions, and small molecules in a solution. Methods have been established to study these solid phase components. Here, we summarized low-throughput experi-mental techniques and high-throughput omics methods in the study of the LST.

Automated summary

Life is composed of functional biomolecules, such as proteins and nucleic acids, which can undergo liquid-liquid phase separation to form liquid droplets. These droplets can transition into solid-like biomolecular condensates, which exist in physiological and pathological conditions. The formation of solid-like condensates, also known as detergent-insoluble aggregates, is not fully understood. Recent research has shown that the transition from a liquid to solid phase is crucial for the formation of these condensates. This review summarizes the sequence regions and solution conditions that impact the phase transition, as well as the methods used to study solid phase components.