Researchers have created the first map of lipid transport in cells

Lipids form the membranes that surround the cell and separate its internal compartments from one another. These membranes give each compartment its own identity and make normal cell function possible. For this system to work, lipids must be continuously and precisely transported between different membranes – a process scientists have long had only limited understanding of.

Now, we know a little more.

Like private chauffeurs

In a new study published in Nature, researchers from the University of Geneva (UNIGE), the European Molecular Biology Laboratory (EMBL) and the University of Bergen present the first large-scale “map” of lipid transport in human cells. The study shows that lipids are not transported at random. Instead, each lipid depends on a limited number of specific transport proteins.

This type of transport is more like private chauffeurs than public transport. Each lipid is recognised by specific proteins that deliver it to the correct destination.

“Cells contain thousands of different lipids, and each membrane needs the right ones to maintain its properties. If lipids end up in the wrong place, the consequences for the cell can be severe,” says professor of Computational Chemistry Nathalie Reuter at the University of Bergen.

Lipids cannot move freely through the watery interior of the cell. They must be shielded and carried by specialised proteins known as lipid transfer proteins. Although these proteins have been known for decades, scientists have had little insight into which lipids they transport and why.

First study of its kind

To gain a better understanding of this process, researchers at the University of Geneva and EMBL used two experimental approaches. They studied lipid transfer proteins directly in human cells and in artificial membrane systems, and used mass spectrometry to identify which lipids were bound to the proteins. In total, they analysed 35 proteins and hundreds of lipid–protein combinations, many of which had not been identified before.

“This is the first study of its kind at this scale. It gives us a real map of the traffic inside cells — who transports what, and where,” Reuter says.

Advanced computer models

To understand why certain proteins select specific lipids, Reuter’s research group at the University of Bergen contributed advanced molecular modelling and simulations. Using detailed 3D computer models, the researchers were able to examine how lipids fit into small binding pockets in the proteins, down to the atomic level.

“These processes are simply too small and too dynamic to be observed directly,” Reuter explains.

“Without modelling and simulations, we would not be able to explain how these proteins recognise the correct lipids and ignore others,” she says.

An important resource

The results show that lipid transfer proteins are often selective not only for certain types of lipids, but also for subtle differences in their chemical structure. Some proteins can bind a group of related lipids, while others depend on additional “helper” lipids that regulate when and where transport takes place.

By providing a map of lipid–protein interactions, the study offers an important resource for further research. Disrupted lipid transport is linked to a range of genetic, metabolic and neurodegenerative diseases, and increased knowledge of these transport systems may help connect molecular mechanisms to disease processes.

“We are still only at an early stage in understanding how lipid transport works in cells. But having this kind of map fundamentally changes which questions we can ask next,” Reuter says.

Reference

Titeca, K., Chiapparino, A., Hennrich, M.L. et al. Systematic analyses of lipid mobilization by human lipid transfer proteins. Nature, 2026.