Jangwon Bae - Biomolecular Condensates?

Understanding Biomolecular Condensates:

The Cell's Dynamic Droplets

Cells organize their chemistry in more than one way. Some compartments, such as the nucleus and mitochondria, are enclosed by membranes. Others form without a surrounding membrane as specific proteins, nucleic acids, and other molecules gather into concentrated, dynamic assemblies.

These assemblies are known as biomolecular condensates. Many arise through phase separation, allowing cells to assemble and reorganize these compartments as conditions change. By selectively concentrating molecules, biomolecular condensates help control where and when biochemical reactions take place.

1. The "Salad Dressing" Analogy

Oil and vinegar provide a simple analogy. After the mixture is shaken, droplets can form and remain distinct from their surroundings. This separation of one liquid into two distinct liquid phases is called liquid-liquid phase separation (LLPS).

A similar process can occur inside cells. Interactions between proteins, RNA, and other molecules can drive LLPS, bringing selected components together into concentrated compartments called biomolecular condensates.

Unlike oil droplets, however, biomolecular condensates are complex and dynamic. Their components can continually move in and out as cellular conditions change.

2. Rooms Without Walls

Membrane-bound organelles are surrounded by membranes that separate their contents from the rest of the cell. Biomolecular condensates, by contrast, can organize molecules without building a physical boundary. Networks of weak, reversible interactions help hold their components together. Molecules can move in and out, enabling condensates to form, reorganize, or dissolve in response to changing cellular conditions.

3. Why Do Cells Use Them?

Why doesn’t the cell simply separate everything with membranes? Because biomolecular condensates give cells a few useful “superpowers”:

Regulating chemical reactions: By gathering proteins that need to work together in one droplet, condensates can help them find one another more easily than if they were scattered throughout the cell.
Responding to stress: When a cell becomes too hot or runs low on nutrients, it can rapidly form condensates called stress granules. These temporary shelters reorganize RNA and proteins, helping the cell protect important resources and adapt until conditions improve.
Switching processes on and off: Many condensates are highly dynamic. They can assemble or dissolve rapidly in response to cellular signals, allowing the cell to turn certain processes on or off when needed.

However, concentrating molecules does not always make a reaction faster. Depending on their composition and physical properties, condensates can enhance, inhibit, or redirect biochemical reactions.

4. When Condensates Go Wrong

Biomolecular condensates are essential for healthy cells, but they can also have a “dark side.” Because they concentrate large numbers of proteins and other molecules, their composition and physical properties must be carefully controlled.

Some condensates can gradually lose their dynamic character and become more solid or aggregate-like, much as liquid honey can eventually form sugar crystals. When this process is not properly regulated, the resulting assemblies may disrupt cellular functions or become toxic.

These changes are being studied in several neurodegenerative diseases:

- Amyotrophic lateral sclerosis (ALS)

- Alzheimer’s disease

- Parkinson’s disease

Condensate dysfunction may also contribute to other diseases. In cancer, abnormal condensates can strengthen signals that promote uncontrolled cell growth. During viral infections, some viruses create condensate-like “replication factories” that help copy their genomes and organize viral components. The immune system also uses condensate formation to coordinate and amplify signals, but poorly regulated assembly may contribute to chronic inflammation or autoimmune disease.

These connections do not provide a single explanation for any disease, and many questions remain. By learning how condensates form, function, and change over time, researchers hope to identify new strategies for preventing or treating disease.

Line and area chart showing PubMed records that explicitly mention biomolecular condensate or biomolecular condensates in the title or abstract, rising from 3 in 2017 to 635 in 2025.

5. A Rising Star in Science

If it seems as though biomolecular condensates and phase separation are appearing everywhere in science, you are not imagining it. What began as a specialized topic has rapidly grown into a major research field spanning cell biology, physics, medicine, and bioengineering.

In 2025, the field received further recognition when Clarivate named Clifford Brangwynne, Anthony Hyman, and Michael Rosen as Citation Laureates in Chemistry for their discoveries on the role of phase-separated biomolecular condensates in cellular organization.

📅 From Discovery to Rapid Growth

Scientists have observed distinct “spots” and membraneless structures inside cells for more than a century. Only recently, however, have researchers begun to understand the physical principles that allow many of these structures to form and function.

2009 — A spark for the field: A landmark study showed that P granules in C. elegans behave like liquid droplets, helping establish phase separation as an important principle of cellular organization.
2017 — A shared language emerges: The influential review “Biomolecular Condensates: Organizers of Cellular Biochemistry” helped bring diverse observations together under a common framework and vocabulary.
2025 — Global recognition: More than 500 papers published that year explicitly mentioned biomolecular condensates. The selection of three pioneering researchers as Clarivate Citation Laureates further highlighted the field’s scientific impact.

📈 Why Is the Field Growing So Quickly?

Biomolecular condensates sit at the intersection of chemistry, physics, biology, medicine, and AI. Chemistry explains the molecular interactions that bring proteins and nucleic acids together, while physics describes how these molecules separate into dynamic compartments. Biology reveals how cells use condensates to organize reactions and respond to change, and medicine investigates what happens when their formation or behavior becomes dysregulated.

AI adds another layer by helping researchers analyze complex data, predict molecules that may form condensates, and design new experiments or therapeutic strategies. By connecting these different perspectives, condensate research offers a shared framework for understanding how molecular interactions shape cellular organization, health, and disease.

Summary

Biomolecular condensates remind us that the cell is not simply a rigid machine, but a dynamic and fluid environment. Through the physical tendency of molecules to gather and separate, cells can create membraneless compartments that organize proteins and nucleic acids, regulate biochemical reactions, and respond rapidly to changing conditions. In this sense, biomolecular condensates represent one of nature’s complex and elegant ways of organizing life through physical principles that may appear remarkably simple.

When condensate formation or behavior becomes disrupted, it may contribute to neurodegeneration, cancer, infection, and immune dysfunction. Positioned at the intersection of chemistry, physics, biology, medicine, and AI, this rapidly growing field provides a powerful framework for understanding how molecular interactions shape cellular organization, health, and disease.

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