If we want to understand what happens in a disease and what goes wrong, we need to know exactly what molecules are involved. This new technique gives us the tools to do that. It could be used to reveal a whole new layer of how proteins are regulated by lipids, which we haven’t been able to study before.
Professor Ulrike Eggert, Professor of Chemical Biology at King’s
22 April 2026
Researchers develop new technique to understand how lipids interact with proteins in living cells
Researchers at King’s College London have developed a new method to study how lipids interact with proteins in living cells, helping to shed light on why our cells produce such a wide diversity of lipids.
Lipids are essential molecules, largely found in cell membranes along with proteins, where they support many vital biological processes such as energy storage and hormone production. Cholesterol is one of the most familiar examples.
Lipids are important for health, and changes in lipids are associated with a wide range of diseases, including cancer and neurodegenerative diseases.
The body produces up to 10,000 chemically distinct lipids. While they are known to be crucial for our health and cellular function, it remains unclear why such a vast diversity is required or why the body invests so much energy in producing so many different types.
The researchers’ hypothesis was that cell membranes contain many highly specialised lipid environments, where particular lipids interact with specific proteins in defined locations in the cell membrane, so that the cell can function properly.
To test this, the study, published in Nature Cell Biology, aimed to develop a method capable of capturing and identifying the lipids associated with individual proteins in the cell membranes of living cells.
The team designed a technique that attaches a molecular “hook” to a specific protein, allowing it to be “pulled out” of the cell, along with the lipids that are attached to it. Using mass spectrometry, a technique that identifies molecules by measuring their mass and chemical composition, they were able to identify the lipids interacting with that protein.
Using this approach, the researchers showed that different proteins are indeed associated with distinct sets of lipids. They also found that these associations change depending on cellular conditions. For example, the same protein was found to interact with different lipids in dividing cells compared to non-dividing cells. This confirms that lipid–protein interactions are specific and dynamic, rather than random.
Professor Ulrike Eggert, Professor of Chemical Biology at King’s and senior author of the paper, said: “We’re interested in understanding what lipids do in cells, particularly as most diseases are associated with changes in lipids. However, because we haven’t had the techniques to study the huge diversity of lipids that exist, we haven't been at a stage where we can easily identify which ones are involved in particular diseases."
The new technique provides a valuable tool for future research. By enabling scientists to identify which lipids interact with specific proteins, it could help improve understanding of how these interactions change in disease. In the longer term, this may support the development of more targeted treatments.
“We used HeLa cells to develop the technique, which are commonly used in laboratory experiments,” added Professor Eggert, “but the beauty of the technique is that it will work in any cell line that can be manipulated to produce a protein with the molecular hook attached.”
The researchers hope that this approach will be widely adopted, allowing scientists to explore lipid–protein interactions across different cell types and conditions, and uncover a previously hidden layer of cellular regulation.
The research was supported by Wellcome and the UKRI- Biotechnology and Biological Sciences Research Council.
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Professor of Chemical Biology