Many of the most important working parts of a cell have no membrane at all. Ribosomes, centrosomes, the nucleolus, stress granules, the cytoskeleton, and proteasomes all function without a lipid bilayer enclosing them. While biology textbooks spend a lot of time on membrane-bound organelles like mitochondria and the nucleus, a growing appreciation for membraneless structures has reshaped how scientists think about cellular organization. These structures stay organized through protein-protein interactions, the physical chemistry of phase separation, or both, and they turn out to be central to everything from cell division to gene expression to disease.
The Nucleolus
The nucleolus is probably the most familiar membraneless structure inside a cell. Sitting within the nucleus, it is the factory where ribosomal components are assembled. It forms around stretches of DNA called nucleolar organizing regions, where the genes encoding ribosomal RNA are clustered.1PubMed Central. New insights into nucleolar structure and function Despite being clearly visible under a microscope as a dense, dark spot, the nucleolus has no surrounding membrane. It holds itself together through a combination of RNA-protein interactions and a physical phenomenon called liquid-liquid phase separation, where certain molecules spontaneously concentrate into droplet-like compartments the way oil separates from water.
The nucleolus is not alone in the nucleus. It belongs to a broader class known as nuclear bodies, which also includes structures like paraspeckles and Cajal bodies. These compartments share a few features: they contain specific RNAs, they behave like liquid droplets, and they rely on proteins with floppy, disordered regions that can make multiple contacts at once.2PubMed. Membraneless nuclear organelles and the search for phases within phases Cajal bodies, for instance, help process the small nuclear RNAs used in gene splicing. None of these structures are enclosed by membranes, yet they maintain distinct identities and compositions within the same nuclear space.
Centrosomes
When a cell divides, it needs a way to pull its chromosomes apart cleanly. That job falls to the mitotic spindle, a structure built from protein filaments called microtubules. The centrosome is the primary organizing center for those microtubules in animal cells. It consists of two barrel-shaped centrioles surrounded by a cloud of proteins called the pericentriolar material, and the whole thing operates without any membrane boundary.3PubMed Central. Pericentriolar material structure and dynamics
The pericentriolar material is what actually concentrates the building blocks for microtubules and launches them outward. It is a dynamic collection of protein complexes, not a fixed bag of molecules sealed inside a lipid shell. This raises an obvious question: what controls its size and shape? Without a membrane to act as a physical fence, the centrosome relies on the organized layering and scaffolding of its protein components to define its edges.4PubMed Central. Recent advances in pericentriolar material organization: ordered layers and scaffolding gels The result is an organelle that can rapidly expand as a cell prepares to divide and then shrink back down afterward, a trick that would be much harder if a rigid membrane had to grow and contract in lockstep.
Ribosomes and Proteasomes
Ribosomes are the molecular machines that read messenger RNA and stitch together proteins. They are found in every living cell, from bacteria to human neurons, and none of them are wrapped in a membrane. Each ribosome is a complex of RNA molecules and dozens of proteins that snap together into a functional unit. In eukaryotic cells, the ribosomal subunits are assembled inside the nucleolus and then exported into the cytoplasm where they do their work. Some ribosomes float freely in the cytoplasm; others attach to the outer surface of the endoplasmic reticulum to feed newly made proteins directly into that membrane system. But the ribosome itself remains membraneless.
Proteasomes are, in a sense, the opposite of ribosomes. Instead of building proteins, they break them down. When a protein is damaged, misfolded, or simply no longer needed, the cell tags it for destruction and feeds it into a proteasome. Proteasomes are found in all three domains of life and are self-compartmentalized, meaning their active protein-chopping parts are sealed inside a barrel-shaped protein shell rather than a lipid membrane.5Nature Reviews Microbiology. Proteasomes and protein conjugation across domains of life This protein-walled design ensures that only targeted proteins get degraded, preventing the proteasome from chewing up everything it bumps into.
Stress Granules and Processing Bodies
Cells encounter all sorts of trouble: heat shock, viral infection, nutrient deprivation, toxic chemicals. When things go wrong, cells often slam the brakes on protein production to conserve resources. The stalled messenger RNAs and their associated proteins do not simply float around aimlessly. Instead, they coalesce into visible cytoplasmic clumps called stress granules. These granules form through phase separation: the RNA-protein complexes stick to one another and condense out of the surrounding cytoplasm the way fog droplets form from humid air.6Molecular Cell. The Proteomic Landscape of Mammalian Stress Granules and Processing Bodies
Processing bodies, or P-bodies, are a related but distinct type of membraneless condensate. They contain mRNAs that are translationally silent and lack the initiation factors needed to restart protein production. While stress granules form in response to acute trouble and dissolve once the crisis passes, P-bodies exist even in unstressed cells and are involved in mRNA storage and decay. Both structures are excellent examples of how cells create internal compartments on the fly, without having to build new membranes, simply by tuning the interactions among their molecular contents.
The Cytoskeleton
The cytoskeleton is not a single structure but a network of filamentous polymers that spans the interior of eukaryotic cells. It gives cells their shape, provides tracks for transporting cargo, and generates the forces needed for movement and division.7PubMed Central. Cell mechanics and the cytoskeleton The three main types of cytoskeletal filament are actin filaments, microtubules, and intermediate filaments. None are enclosed by membranes; they are open polymers built from repeating protein subunits that can assemble and disassemble rapidly.
Cilia and flagella, the whip-like projections that some cells use to swim or move fluid, extend from the cytoskeleton. Their core structure, the axoneme, is a bundle of microtubule doublets arranged in a characteristic ring pattern.8PubMed Central. Axoneme Structure from Motile Cilia The axoneme is anchored to the cell by a basal body, which is structurally related to a centriole. Although the outer surface of a cilium is covered by the cell’s plasma membrane, the internal axoneme itself is a membraneless assembly of proteins and microtubules. The distinction matters because the axoneme can be remodeled without rebuilding its membrane covering; some organisms switch their flagellar axoneme from one structural arrangement to another depending on environmental conditions.9Nature Communications. Basal body multipotency and axonemal remodelling are two pathways to a 9+0 flagellum
Vault Complexes
Vaults are among the stranger membraneless structures in eukaryotic cells. They are massive ribonucleoprotein particles, barrel-shaped and hollow, found in the cytoplasm of organisms from slime molds to humans. Each vault is built from two half-shells that fit together like the halves of a rugby ball. A single half-shell contains 39 copies of a protein called major vault protein, which folds into multiple domains that interlock to form the cage.10PubMed Central. Structural studies of large nucleoprotein particles, vaults The interior is spacious enough to hold other molecules, and the structure also contains small RNAs and enzymes.
Despite decades of study, the precise function of vaults remains surprisingly unclear. Their hollow architecture and ability to open and close has led to proposals that they serve as intracellular transport vehicles, shuttling cargo between compartments.11PubMed Central. Structural flexibility of the human vault particle revealed by high-resolution cryo-EM and molecular dynamics simulations Other researchers have suggested they might sequester specific molecules to keep them away from the wrong biochemical reactions.12PubMed. Structure of the vault, a ubiquitous celular component Vaults are highly conserved across evolution and extremely abundant in some cell types, which suggests they do something important. They just seem to be keeping the secret well. What is clear is that their enclosure is made entirely of protein, not lipid, placing them firmly in the membraneless category.
Membraneless Structures in Bacteria
Bacteria were long thought to be simple bags of molecules with minimal internal organization. That picture has been thoroughly revised. Bacterial cells contain several types of membraneless structures, the most conspicuous being the nucleoid, a condensed mass of genomic DNA that occupies a distinct region of the cell. Unlike a eukaryotic nucleus, the nucleoid has no surrounding membrane.13PLOS Genetics. Architecture of the Escherichia coli nucleoid Its organization is maintained by specialized proteins that compact and remodel the DNA, as well as by DNA supercoiling and active transcription, which together produce a dynamic, highly ordered structure.14PubMed. The bacterial nucleoid: a highly organized and dynamic structure
Recent work has shown that the nucleoid is not merely organized; it actually forms a phase-separated domain. The DNA-rich nucleoid and the ribosome-rich cytoplasm around it behave as two distinct liquid-like phases within the cell. Transcription along the boundary between them helps enforce this segregation, keeping the information-storage zone (the DNA) physically apart from the protein-production zone (the ribosome-dense cytoplasm).15PubMed Central. Bacterial nucleoid is a riddle wrapped in a mystery inside an enigma
Bacteria also build microcompartments out of protein shells. These are not true membranes made of lipids; they are icosahedral cages assembled from interlocking protein tiles. Carboxysomes, for example, are protein-shelled compartments found in cyanobacteria that encapsulate the enzymes responsible for carbon fixation, concentrating carbon dioxide around the key enzyme and boosting its efficiency.16PubMed Central. Comparative analysis of carboxysome shell proteins Other bacterial microcompartments handle different metabolic tasks, from breaking down certain carbon sources to neutralizing toxic intermediates.17PubMed. Structure of a Minimal α-Carboxysome-Derived Shell and Its Utility in Enzyme Stabilization The shell is selectively permeable, allowing substrates in and products out while keeping the internal chemistry separate from the rest of the cytoplasm. Bacteria even form liquid-like protein aggregates called aggresomes during stress, and these too behave as phase-separated droplets consistent with membraneless condensate physics.18Science Advances. Membraneless organelles formed by liquid-liquid phase separation increase bacterial fitness
How Phase Separation Holds It All Together
The recurring theme across many of these structures is liquid-liquid phase separation. The cell’s interior is not a uniform soup; it is more like a salad dressing that has been shaken but is already starting to separate. Certain proteins and RNAs, especially those with intrinsically disordered regions or repetitive interaction motifs, spontaneously demix from the surrounding cytoplasm and concentrate into droplet-like compartments. These compartments are now collectively called biomolecular condensates.19PubMed. Liquid-liquid phase separation in biology: mechanisms, physiological functions and human diseases
The advantage of condensates over membrane-bound compartments is speed and flexibility. A condensate can form in seconds when conditions change, dissolve just as quickly when the signal passes, and selectively concentrate some molecules while excluding others based purely on chemical compatibility. The nucleolus, stress granules, P-bodies, and many nuclear bodies all work this way. Beyond mere organization, concentrating enzymes and their substrates into condensates can actually accelerate biochemical reactions. Laboratory experiments using artificial condensates have shown that compartmentalizing an enzyme away from an excess of its substrate can relieve a common form of inhibition and dramatically speed up the reaction.20PubMed Central. Membrane-less compartmentalization facilitates enzymatic cascade reactions and reduces substrate inhibition
Cells tune their condensates through a variety of levers. Post-translational modifications on proteins, such as phosphorylation, can shift the threshold at which phase separation occurs, causing a condensate to form or dissolve. RNA levels matter too: add more RNA and you may drive assembly; degrade it and the condensate falls apart. These regulatory mechanisms allow cells to maintain a repertoire of membraneless compartments whose existence and composition change with the cell’s needs.21PubMed Central. The molecular language of membraneless organelles
Algal Pyrenoids
Plants and algae have their own membraneless structures adapted to photosynthesis. The pyrenoid, found in many algae and some land plant relatives, is a membraneless organelle inside the chloroplast that concentrates the carbon-fixing enzyme Rubisco. Given that Rubisco is notoriously slow and easily confused by oxygen, packing it into a dense, COâ‚‚-enriched compartment dramatically improves its performance. The pyrenoid is estimated to be responsible for a large share of global carbon fixation, making it one of the most ecologically consequential membraneless structures on the planet. Recent structural and proteomic work has transformed it from an overlooked curiosity into a focal point of photosynthesis research.
When Membraneless Structures Go Wrong
The same physical properties that make condensates useful also make them vulnerable to malfunction. A liquid-like droplet can, under the wrong conditions, harden into a gel or a solid aggregate. This transition is increasingly recognized as an early event in several neurodegenerative diseases.22PubMed Central. Beyond aggregation: Pathological phase transitions in neurodegenerative disease Proteins associated with amyotrophic lateral sclerosis (ALS) and frontotemporal dementia, for example, are often found in stress granules. Mutations in these proteins can cause stress granules to lose their liquid character and solidify into the kind of insoluble aggregates seen in patient brain tissue.
Misfolded proteins that accumulate inside stress granules can decrease the internal dynamics of the granule and trigger an aberrant transition from liquid to solid.23PubMed Central. An aberrant phase transition of stress granules triggered by misfolded protein and prevented by chaperone function Cells normally prevent this with molecular chaperones, proteins that refold or clear out problematic molecules. When that quality-control system is overwhelmed, condensates that should be temporary and reversible become permanent and toxic. The recognition that disease-related protein aggregation may begin as a corrupted phase transition, rather than a simple precipitation event, has opened new therapeutic avenues. If you can keep a condensate in its healthy liquid state or help it dissolve on schedule, you might prevent the downstream damage.
Engineering Membraneless Compartments
The principles behind biological condensates have caught the attention of bioengineers. If cells naturally build membraneless compartments to concentrate enzymes and channel metabolic reactions, could you design artificial ones to boost the production of useful chemicals? The answer, increasingly, is yes. Researchers have built synthetic membraneless organelles inside yeast cells by introducing engineered disordered protein sequences that self-assemble into condensates. By tuning the size and rigidity of these artificial compartments, they were able to shift how the yeast cell routes its metabolism, increasing the yield of target chemicals and reducing wasted carbon released as COâ‚‚.24PubMed. Engineered Artificial Membraneless Organelles in Saccharomyces cerevisiae To Enhance Chemical Production
Other groups have gone further, engineering condensates that respond to external signals. One team created synthetic membraneless organelles whose physical state can be switched by exposure to red light, triggering them to transition from liquid to solid on command.25Nature Communications. Controlling synthetic membraneless organelles by a red-light-dependent singlet oxygen-generating protein Beyond industrial biotechnology, such systems could serve as tools for studying how condensate aging and solidification work at the molecular level, with potential relevance to the disease processes described above.
Membraneless Compartments and the Origin of Life
One of the deepest questions about membraneless organization is whether it predates membranes altogether. Modern cells rely on lipid bilayers to define themselves, but lipid membranes are complex structures that require their own biosynthetic machinery. Before that machinery existed, early chemical systems on Earth may have used simpler forms of compartmentalization. Researchers have shown that alpha-hydroxy acids, molecules that are produced alongside amino acids under prebiotic conditions, can spontaneously polymerize and form membraneless microdroplets capable of concentrating other molecules inside them.26PubMed Central. Membraneless polyester microdroplets as primordial compartments at the origins of life
RNA molecules, central to many origin-of-life scenarios, are also capable of driving phase separation. Given the diversity of both biological and nonbiological molecules that undergo liquid-liquid phase separation, membraneless compartments may have played key roles in prebiotic chemistry well before the first true cell membrane ever formed.27Biochemistry. Physical Principles and Extant Biology Reveal Roles for RNA-Containing Membraneless Compartments in Origins of Life Chemistry If this picture is correct, the membraneless compartments inside your cells today are not evolutionary afterthoughts bolted onto a membrane-first system. They may be echoes of the very first form of biological organization, older than membranes themselves and still carrying out indispensable work four billion years later.