Researchers developed a marker that localizes selected proteins in cells with nanometre precision. This highly specific lock-and-key element consists of the small synthetic molecule trisNTA and a genetically encoded His-tag.

In order to deliver this protein marker into cells, the researchers applied a procedure in which a mixture of cells together with the marker were forced through narrow constrictions. This process is called cell squeezing. Under pressure, the cells incorporate the fluorescent probes with an efficiency rate greater than 80 percent. In addition, the process enabled to squeeze one million cells per second through the artificial capillary in high-throughput.

Since the marker binds very efficiently and specifically to the target protein and its concentration can be precisely regulated within the cell, the researchers were able to record high resolution microscopy images in living cells. Moreover, they were able to trace proteins with the marker only when activated by light. Thus, cellular processes can be observed with high precision in terms of space and time.

The researchers can even combine their labeling methods with other protein labeling techniques in living cells to observe several proteins simultaneously in real time.