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Mysterious droplets inside cells: How is phase separation changing biology?
In the field of biochemistry, biomolecular condensates are a class of membraneless organelles and organelle subdomains that are responsible for performing specialized functions within the cell. The composition of these condensates is not controlled by the boundary membrane, but instead forms and maintains tissue through a variety of different processes. The best-known process is the phase separation of proteins, RNA, and other biological macromolecules to form aggregates such as colloidal emulsions, gels, liquid crystals, solid crystals, or intracellular aggregates.
The emergence of biomolecular condensates has completely changed our understanding of the internal structure and function of cells.
Historical background
Microcell theory
Microcell theory was proposed by Carl Negelli in 1858, who studied starch granules in detail. He believed that amorphous substances such as starch and cellulose were composed of building blocks arranged in loose crystals to form microcells. Water can penetrate between these microcells, and new microcells can form between old microcells. This model has been used not only to describe the swelling of starch granules, but also for cellulose in plant cell walls.
Colloidal phase separation theory
In the late 19th century, William Bate Hardy and Edmund Beecher Wilson described the cytoplasm (then called "protoplasm") as a colloid. In his study of globulin, Hardy linked the formation of biological colloids to phase separation, emphasizing how colloidal particles disperse in solvents and form internal phases. In subsequent studies, scientists began to re-examine the importance of phase separation in the internal structure of cells.
Review of phase separation
As confocal microscopy improved in the late 20th century, researchers discovered that proteins, RNA, or carbohydrates could be concentrated in many membraneless groups of cells. During this period, the concept of phase separation was reintroduced into cell biology, and the concept of phase separation of biological macromolecules within cells was proposed.
Examples of phase separation
Cytoplasmic condensates
Many condensates found in the cytoplasm, such as Lewy bodies, stress granules, P granules, etc., are formed via liquid-liquid or liquid-solid phase separation. These structures have important biological functions within cells, and their morphological and dynamic characteristics are receiving more research attention.
Intranuclear condensates
Nucleoli, nuclear speckles, and other intranuclear structures are also thought to form by phase separation mechanisms similar to those within the cytoplasm, again targeting the category of biomolecular condensates.
The role of phase separation in biology
Phase separation is regarded as the core of intracellular synergy, and many biological processes such as signal transduction, gene expression regulation, etc. have been shown to be related to fibrillar structures and droplet phase separation. For example, the supramolecular complex in the Wnt signaling pathway consists of Dsh protein through phase separation and aggregation, thereby playing an important role in signal transmission.
Many phase separation processes are closely linked between cellular health and disease states, and the exploration of disease is becoming an important direction for future biomedical research.
Synthetic biomolecular condensates
In synthetic biology, scientists have begun to develop synthetic biomolecular condensates that can be used to explore cellular organization and function. Through flexible design and control, synthetic condensates can provide reactivity, efficiency, and regulatory capabilities and may be used as drug delivery platforms.
Research methods
To gain a deeper understanding of the dynamic properties of these biomolecular condensations and the basic operating principles of cells, scientists use a variety of techniques to observe and study, including high-resolution microscopy, protein labeling, and live-cell imaging. These methods allow them to track and Manipulating the behavior of condensates further advances advances in biology and medicine.
As our understanding of biomolecular condensates deepens, we may be able to more clearly explore their role in biology in the future, and may even open up new ideas for treating various diseases. How much influence do these mysterious structures in the liquid state have on the operation of life?
