Biomolecular condensates are a class of non-membrane bound organelles and organelle subdomains. As with other organelles, biomolecular condensates are specialized subunits of the cell. Unlike many organelles, biomolecular condensate composition is not controlled by a bounding membrane. Instead they are formed by phase separation of proteins and other biopolymers into a colloidal emulsion or gel-sol, which is determined by the physical chemistry of these polymers. Colloidal behaviour is generated by the clustering, oligomerisation or polymerisation of various biomolecules within the cytosol to drive either liquid-liquid, liquid-gel, or liquid-solid phase separation. Biomolecular condensation is a form of self-assembly or self-organisation and is strongly enhanced by macromolecular crowding.
The concept of biomolecular condensates as an organising principle for the compartmentalisation of living cells dates back to the 19th Century, beginning with William Bate Hardy and Edmund Beecher Wilson describing 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. More recently, the term phase separation was borrowed from polymer physics and colloidal chemistry to describe the colloidal segregation of the cytoplasm  and nucleus. The newly coined term 'biomolecular condensate' selectively refers to biological polymers (as opposed to synthetic polymers) undergoing colloidal phase separation, which is analogous to condensation - a colloidal form of gas-liquid phase transition and subsequent separation.
In physics, condensation often means a gas-liquid phase transition, while in biology the term 'condensation' is used much more broadly and can also refer to liquid-liquid, liquid-gel, or liquid-solid phase separation, as well as liquid-to-solid phase transitions such as DNA condensation during prophase of the cell cycle or protein condensation of crystallins in cataracts  - hence the use of 'biomolecular condensate' to broadly describe biological colloids of many different types.
Liquid droplets in cells
The term biomolecular condensate is not universally applied, and some non-membrane bound structures are just referred to as liquid droplets, or referred to as the product of liquid-liquid phase separation (LLPS) . These structures look like the analog of oil droplets in water, i.e., of the cytoplasm or nucleoplasm undergoing liquid-liquid phase separation. The two terms biomolecular condensate and intracellular liquid droplet are often interchangeable, although liquid droplets do have to have the properties of a liquid, while biomolecular condensates may also be more solid or gel-like. In that sense biomolecular condensate may be a more general term, while liquid droplets are a sub-class of biomolecular condensate. The terms 'puncta' or 'dots' were also used, particularly in early studies  to describe the same type of structures. Droplets of fluorescently-tagged proteins look like bright dots or points (puncta) of light, in a microscope.
One of the first discovered examples of this class of biomolecular condensate were the supramolecular complexes formed by components of the Wnt signalling pathway. The Dishevelled (Dsh) protein undergoes clustering in the cytoplasm  via its DIX domain, which mediates protein polymerisation, and is important for signal transduction. The Dsh protein functions both in planar polarity and Wnt signalling, where it recruits another supramolecular complex (the Axin complex) to Wnt receptors at the plasma membrane. The formation of these Dishevelled and Axin containing droplets is conserved across metazoans, including in Drosophila, Xenopus, and human cells.
Another example of liquid droplets in cells are the germline P granules in Caenorhabditis elegans. These granules separate out from the cytoplasm and form droplets, as oil does from water. Both the granules and the surrounding cytoplasm are liquid in the sense that they flow in response to forces, and two of the granules can coalesce when they come in contact. When (some of) the molecules in the granules are studied (via fluorescence recovery after photobleaching), they are found to rapidly turnover in the droplets, meaning that molecules diffuse into and out of the granules, just as expected in a liquid droplet (but not necessarily for droplets of oil in water, or gel-like droplets). The droplets can also grow to be many molecules across (micrometres) Studies of droplets of the Caenorhabditis elegans protein LAF-1 in vitro also show liquid-like behaviour, with an apparent viscosity Pa s. This is about a ten thousand times that of water at room temperature, but it is small enough to enable the LAF-1 droplets to flow like a liquid.
Cytoplasmic biomolecular condensates arising by either liquid-liquid, liquid-gel or liquid-solid phase separation:
- Lewy bodies
- Stress granule
- Germline P-granules
- Lipid droplets
- Starch granules
- Glycogen granules
- Corneal lens formation and cataracts
- Other cytoplasmic inclusions such as pigment granules or cytoplasmic crystals
- Misfolded protein aggregation such as amyloid fibrils
- Membrane protein, or membrane-associated protein, clustering at neurological synapses, cell-cell junctions, or other membrane domains.
- Other large multiprotein complexes or supramolecular assemblies in signal transduction.
It can also be argued that cytoskeletal filaments form by a polymerisation process similar to phase separation, except ordered into filamentous networks instead of amorphous droplets or granules.
As colloidal phase separation involves oligomeric or polymeric interactions between an indefinite number of components, it is generally considered distinct from formation of smaller protein complexes with defined numbers of subunits, such as viral capsids or the proteasome - although both are examples of spontaneous self-assembly or self-organisation.
Nuclear biomolecular condensates:
Other nuclear structures including heterochromatin and DNA condensation in condensed mitosis chromosomes form by mechanisms similar to phase separation, so can also be classified as biomolecular condensates.
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