In biochemistry, biomolecular condensates are a class of membrane-less organelles and organelle subdomains, which carry out specialized functions within the cell. Unlike many organelles, biomolecular condensate composition is not controlled by a bounding membrane. Instead, condensates can form and maintain organization through a range of different processes, the most well-known of which is phase separation of proteins, RNA and other biopolymers into either colloidal emulsions, gels, liquid crystals, solid crystals or aggregates within cells.
History
Micellar theory
The micellar theory of Carl Nägeli was developed from his detailed study of starch granules in 1858. Amorphous substances such as starch and cellulose were proposed to consist of building blocks, packed in a loosely crystalline array to form what he later termed “micelles”. Water could penetrate between the micelles, and new micelles could form in the interstices between old micelles. The swelling of starch grains and their growth was described by a molecular-aggregate model, which he also applied to the cellulose of the plant cell wall. The modern usage of 'micelle' refers strictly to lipids, but its original usage clearly extended to other types of biomolecule, and this legacy is reflected to this day in the description of milk as being composed of 'casein micelles'.
Colloidal phase separation theory
The concept of intracellular colloids as an organizing principle for the compartmentalization of living cells dates back to the end of the 19th century, beginning with William Bate Hardy and Edmund Beecher Wilson who described the cytoplasm (then called 'protoplasm') as a colloid. Around the same time, Thomas Harrison Montgomery Jr. described the morphology of the nucleolus, an organelle within the nucleus, which has subsequently been shown to form through intracellular phase separation. WB Hardy linked formation of biological colloids with phase separation in his study of globulins, stating that: "The globulin is dispersed in the solvent as particles which are the colloid particles and which are so large as to form an internal phase", and further contributed to the basic physical description of oil-water phase separation.
Colloidal phase separation as a driving force in cellular organisation appealed strongly to Stephane Leduc, who wrote in his influential 1911 book The Mechanism of Life: "Hence the study of life may be best begun by the study of those physico-chemical phenomena which result from the contact of two different liquids. Biology is thus but a branch of the physico-chemistry of liquids; it includes the study of electrolytic and colloidal solutions, and of the molecular forces brought into play by solution, osmosis, diffusion, cohesion, and crystallization."
The primordial soup theory of the origin of life, proposed by Alexander Oparin in Russian in 1924 (published in English in 1936) and by J.B.S. Haldane in 1929, suggested that life was preceded by the formation of what Haldane called a "hot dilute soup" of "colloidal organic substances", and which Oparin referred to as 'coacervates' (after de Jong) – particles composed of two or more colloids which might be protein, lipid or nucleic acid. These ideas strongly influenced the subsequent work of Sidney W. Fox on proteinoid microspheres.
Support from other disciplines
When cell biologists largely abandoned colloidal phase separation, it was left to relative outsiders – agricultural scientists and physicists – to make further progress in the study of phase separating biomolecules in cells.
Beginning in the early 1970s, Harold M Farrell Jr. at the US Department of Agriculture developed a colloidal phase separation model for milk casein micelles that form within mammary gland cells before secretion as milk.
Also in the 1970s, physicists Tanaka & Benedek at MIT identified phase-separation behaviour of gamma-crystallin proteins from lens epithelial cells and cataracts in solution, which Benedek referred to as 'protein condensation'.
In the 1980s and 1990s, Athene Donald's polymer physics lab in Cambridge extensively characterised phase transitions / phase separation of starch granules from the cytoplasm of plant cells, which behave as liquid crystals.