Protein Phase Separation and Determinants of in cell Crystallization

Liquid-Liquid Phase Separation (LLPS) in cells is known as a complex physicochemical process causing the formation of membrane-less organelles (MLOs). Cells have well-defined different membrane-surrounded organelles like mitochondria, endoplasmic reticulum, lysosomes, peroxisomes, etc., however, on demand they can create membrane-less organelles as stress granules, nucleoli and P bodies to cover vital functions and regulatory activities. However, the mechanism of intracellular molecule assembly into functional compartments within a living cell remains till now not fully understood. (Soft Matter 2019, 15 (6):1135-1154). In vitro and in vivo investigations unveiled that MLOs emerge after preceding liquid-liquid, liquid-gel, liquid-semi-crystalline, or liquid-crystalline phase separations. Liquid-liquid and liquid-gel MLOs form the majority of cellular phase separation events, while the occurrence of micro-sized crystals in cells was only rarely observed, however can be considered as a result of a preceding protein phase separation event. In vivo, also known and termed as in cellulo crystals, are reported since 1853 (Botanische Zeitung, 13, 881-8 821 855; CR Mem. Soc. Biol. 5, 450-454, 1853). In some cases, they have been linked to vital cellular functions, such as storage and detoxification. However, the occurrence of in cellulo crystals is also associated to diseases like cataract, hemoglobin C diseases etc. (Biology Chemistry De Gruyter 2018, 399 (7):751-752). Therefore, better knowledge about the involved molecular processes will support drug discovery investigations to cure diseases related to in cellulo crystallization. We summarize physical and chemical determinants known today required for phase separation initiation and formation and in cellulo crystal growth. This article is protected by copyright. All rights reserved.