Macro, Mini, Micro

Clever microfluidic platforms take the study of protein-protein interactions to a new level.

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ON-CHIP PROTEIN EXPRESSION: DNA fragments inside the black circles pictured here get turned into two different proteins by pumping a transcription/translation mix through the blue channels. Fluorescent antibodies that glow when protein-protein interactions occur are located in adjacent orange circles.COURTESY OF DORON GERBER/BAR ILAN UNIVERSITYWhen Shirit Einav set out to look for new interactions between membrane-associated proteins, she was quick to skip traditional screening methods. That’s because some of the most popular ones are limited when it comes to studying insoluble membrane proteins, says Einav, an assistant professor of medicine and of microbiology and immunology at Stanford University.

The typical yeast two-hybrid approach, for example, readily detects protein interactions that occur in the nuclei of yeast cells, but it works poorly for membrane proteins, which often have trouble relocating to the nucleus and can be insoluble in this cellular compartment. Another common technique requires purifying membrane protein complexes from mammalian cells, but the methods for doing so often destroy protein interactions. Even soluble proteins can be tough to crack if the proteins are not expressed well in yeast or mammalian cells, or if the interactions are so weak that they break apart during washing steps.

“Microfluidics is one of the most advanced technologies to overcome some of these limitations,” Einav says.

The basic microfluidic setup involves a platform about the size of a ...

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