Scientists at MIT have developed a new way to label proteins in 3D tissues. This technology, called CuRVE, lets them mark millions of cells in a whole mouse brain or other large tissues in just one day. The researchers shared their findings in a paper published in Nature Biotechnology.

By using antibodies that can stick to specific targets, the scientists can see what proteins cells are making. This is important because it shows what jobs cells are doing or how they react to diseases or treatments. However, looking at proteins in thick, whole tissues has been hard.

Before this, scientists had to slice tissues into thin pieces or break them apart to study them. MIT scientists had already made tissues transparent with methods like CLARITY and SHIELD. But they needed a way to label proteins uniformly throughout large tissues. Think of it like marinating a steak; the outside soaks up the flavor fast, but the inside needs more time. The same goes for tissue labeling with large antibody molecules.

Ultra-fast speed

The CuRVE technology, specifically implemented as eFLASH in this project, solves this by controlling how fast antibodies bind to proteins while also speeding up how quickly they spread through the tissue. They use a chemical, deoxycholic acid, to adjust binding speed and change the acidity of the labeling solution. They also use electric fields to push antibodies deeper into the tissue faster.

Using eFLASH, the scientists labeled over 60 different proteins in whole organs like mouse brains, embryos, and even human brain samples, all in a day – an “ultra-fast” speed for whole, intact organs, the scientists said. This is much quicker than before. They also compared their method to another where cells are genetically modified to glow when making a certain protein. They found big differences between the two methods, showing that antibody labeling can give a more accurate picture of protein presence. This could help understand biological processes better, especially where genetic labeling might mislead researchers about protein expression.

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