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Engineers have created a device that could assist in evaluating the safety of new disease treatments.

A research team at Penn State developed a fluorescent sensor that is activated inside a cell when misfolded proteins begin to aggregate, which is an early sign of cellular stress. This prototype is the first of its kind to use a fluorescent sensor that will not turn on until the aggregation process is initiated.

In an experiment of this new technique, researchers designed an unstable protein labeled AgHalo that is tagged with a specialized fluorescent dye that becomes activate in a hydrophobic also known as a water-repellent environment.

Hydrophobic portions of proteins tend to be buried pretty deep in the structure of a properly-folded proteins, since the cell environment is mostly water.

Once the AgHalo protein began to misfold and aggregate, the dye in the sensor can interact with the hydrophobic portions of the protein and begin to fluoresce.

"An additional advantage of our system is that the level of fluorescence is correlated to the amount of protein aggregation in the cell, so we can quantify the level of stress" said first author of the paper Yu Liu, a postdoctoral researcher at Penn State, in a statement. Also, because our method measures the level of fluorescence, rather than having to identify the fluorescence under a microscope, it can be done using more accessible technology, like plate readers, and it is much more high-throughput."

The sensor was tested on the level of protein stress induced by five commonly used anti-cancer drugs.

All five of the drugs produced some level of protein stress detectable by the sensor, but none of the drugs have previously caused significant cell death in previous drug safety tests.

"Because we tested the anti-cancer drugs at much higher doses than typically used for treatment, our results do not necessarily call into question the continued use of these drugs," Liu elaborated. "However, because protein stress from long-term treatments could have lasting effects, evaluating drugs with our new sensor will help in the development of safer drugs."

The technique can be adapted to sense protein aggregates caused by other toxins as well as in diseases like Alzheimer’s and Parkinson’s.

Ultimately, this invention could enable scientists to identify protein stress in cells at much earlier stages and then analyze the mechanisms cells use to combat this stress and create compounds that strengthen the cells ability to withstand this it.

These findings were published in the journal Angewandte Chemie International Edition.

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