Color-Coded Test for Protein Folding

Stanford University scientists have developed a simple test that instantly changes color when a protein molecule attached to a gold nanoparticle folds or unfolds. The new technique works on the same principle as ordinary pH tests that measure the acidity of water. The new sensor may eventually provide biomedical researchers a fast, affordable method for detecting antibodies and other disease-related proteins.

In their experiment, the researchers created a liquid solution containing nano-sized particles of gold saturated with a protein called cytochrome c. The initial batch of gold-cytochrome solution had a rosy red hue and a pH value of 10 – about the same as an over-the-counter heartburn medication. But when drops of hydrochloric acid were added, the solution began to change color, turning purple when the pH reached 5.8 and light blue at pH 4, which is close to the acidity of wine.

Lab analysis revealed that additional hydrochloric acid was causing the cytochrome c molecules to unfold. As a result, gold nanoparticles coated with cytochrome c began clumping together – a process that caused the solution to quickly change from red to blue as the acidity increased.

The researchers were surprised to discover that, when the pH was raised from 4 to 10, the blue solution turned reddish once again – a strong indication that some cytochrome c molecules had refolded into their original 3D shape. In fact, the experiment showed that, when attached to gold film, cytochrome c can fold, unfold, and refold countless times depending on the acidity of the solution, thus making it an ideal tool for detecting conformational changes in proteins.

Find out more at: www.stanford.edu/group/Zarelab