Leiden researchers have discovered a surprising new way to shape and control tiny droplets of molecules found in living organisms. The breakthrough could lead to smarter biomaterials, improve drug delivery and even new insights into the emergence of life on Earth. The work was published in Nature Communications.
Biomolecular condensates are tiny, droplet-like structures made up of molecules that help organise key processes in living organisms. Because they are so small and constantly changing, it has been difficult for scientists to measure their physical properties or control how they behave. Researchers at the Mashaghi Lab now developed a method to make this possible.
Using UV light as a molecular switch
'Our lab works at the interface of biophysics, molecular engineering and medicine', says Mashaghi. 'We explore how molecular interactions drive the emergent properties of biological materials.'
Inside the condensates, Mashaghi and his team triggered a reaction normally associated with DNA damage from UV light (like that seen in skin cancer). Known as thymine dimer formation (see box), this process causes two neighbouring thymine bases to bond together. By harnessing this reaction as a molecular 'switch' within the condensates, the researchers were able to alter the internal connectivity of the molecules, allowing them to control how the condensates behave.
Building on a Dutch legacy
The foundations of this discovery were laid nearly a century ago. In the 1920s, Dutch chemist Hendrik G. Bungenberg de Jong first described how oppositely charged molecules can spontaneously form tiny droplets, known as coacervates. Today, these are considered early models of biomolecular condensates.
Decades later, Dutch photochemist Rob Beukers made another key contribution. He helped uncover how ultraviolet (UV) light can damage DNA, for example, by causing the formation of thymine dimers.
Together, these discoveries laid important groundwork for our current understanding of processes inside living cells.
Watching condensates in action
A key innovation in the study is a new microscope-based technique that directly measures how individual droplets deform and fuse. This technique allows researchers to determine changes in their stiffness, elasticity and viscosity. It also makes it possible to study transitions from liquid-like to gel-like or solid states. In addition to revealing normal condensate behaviour, it also helps researchers study how harmful protein aggregates form in diseases such as Alzheimer's and Parkinson's and muscular dystrophies.
'Light-sensitive condensates can inspire smart materials and help deliver medicines exactly where and when they're needed.'
From smart biomaterials to drug delivery systems
UV light allows researchers to chemically modify and stabilise condensates into compartmentalised structures. Beyond fundamental insights, this control strategy points to exciting opportunities for biomedical and technological applications. For example, light-responsive condensates could inspire smart biomaterials or drug delivery systems. In such a system, drugs could be safely stored and then precisely released in the body on demand using light.
Shedding (UV) light on early life
Interestingly, these findings may also offer clues about how life first emerged on Earth. Scientists think condensates acted as the first proto-cells in early life. Mashaghi: 'We now know that UV light could have helped form and stabilise these structures, creating tiny safe spaces where important biochemical reactions could take place. Unlike the usual harmful effects of UV radiation, this compartmentalisation may have helped early molecules survive intense UV exposure. From the first building blocks of life to the cells in our bodies today, a little light can go a long way.'
Wetenschappelijk artikel
Sheikhhassani, V., Wong, F.H.K., Bonn, D., and Mashaghi, A. Optically driven control of mechanochemistry and fusion dynamics of biomolecular condensates via thymine dimerization. Nat Commun (2026). https://doi.org/10.1038/s41467-026-70757-w
The header image was AI-generated based on the real experimental image.
