Original story from the Max Planck Institute of Molecular Cell Biology and Genetics (Dresden, Germany). An international research team presents a new imaging technique to make lipids in cellular membranes visible and show how they are organized at the nanoscale. Biological membranes of cells and its subunits (organelles) are organized into tiny regions (nanodomains) made up of fats (lipids) and proteins. Those specialized regions carry out important tasks for the cell, such as signaling, sorting or transport. While proteins in these domains are well understood, the lipid distribution and behavior within them remain a bit of a mystery, as lipids move very quickly and existing methods struggle to visualize individual lipid species at high resolution. To localize lipids, researchers use ‘bifunctional lipid probes’, which are very small, slightly modified lipids that act like molecular GPS tags. These probes can be added into living cells, then ‘frozen in place’ with light (photo-crosslinking), and later labeled with fluorescence using a chemical reaction (click chemistry). In this way, researchers can track where specific lipids are and not alter and disturb the cell too much. However, light microscopy alone is not enough to visualize small details in the cell membrane. Higher details can be captured by electron microscopy. Correlative light and electron microscopy (CLEM) combines the strengths of both techniques. Together with the bifunctional lipid probes, Lipid-CLEM shows where labeled lipids are and makes the fine structure of the membranes visible. Previous CLEM methods, though, either damaged the membrane structure, only worked on the…