Scientists have powerful tools to peer inside single cells—but they can only peer so far. Some of a cell’s innermost secrets remain elusive, too small or fleeting to study.

Two Allen Distinguished Investigators are developing a radical new technology to investigate a key biological blind spot. Their goal: stretch cells like Silly Putty, physically enlarging them by up to 20 times. This would hopefully unveil small molecules that act as vital cellular nutrients.

The researchers have dubbed their approach Expansion Mass Spectrometry (ExMS). They plan to use ExMS to study how ovarian cancer cells use nutrients called metabolites to grow and spread.

Metabolites help fuel the chemical reactions inside a cell. But their minuscule size and constant motion have made them difficult to study.

“We just don’t understand where the cell keeps all these molecules that we know are so important,” said Laura Sanchez, Ph.D., an associate professor at the University of California Santa Cruz. “They’re missing from all viewpoints.”

That blind spot matters because metabolites are implicated in cancer and many other diseases, said Lydia Kisley, Ph.D., an assistant professor of physics at Case Western Reserve University. Understanding where they are in a cell, and what the cell is doing with them, could offer a new window into detecting and treating disease.

To open that window, Kisley and Sanchez are merging the worlds of microscopy and mass spectrometry. Both methods have limits when it comes to studying a cell’s nutrients.

Even the most advanced microscopes can only see a handful of metabolites at any one time; scientists estimate our cells have tens of thousands. Mass spectrometry analyzes molecules by their mass and can measure many metabolites at once, but it doesn’t work at the single-cell level.

ExMS aims to combine the two approaches and literally stretch our ability to sense nutrients to new limits.

Kisley’s lab has spent the past year building the cell stretcher. Meanwhile, Sanchez has been growing ovarian cancer cells in a special gel that expands like Silly Putty when pulled. After a few hiccups, her lab can now observe key features in the ovarian cancer cells like invadopodia—small, lasso-like projections these cells use to invade neighboring tissues.

The next step will be to apply the cell-stretching technique to these cells. While they are hopeful ExMS can help map and measure metabolites, the researchers aren’t exactly sure what will happen.

“The cells could explode,” Kisley admits.

But even failed attempts could offer clues into how cancer cells manipulate nutrients to spread throughout the body, she added.

“Sometimes when we talk about the project, people are like, ‘that sounds so crazy,’” Sanchez said.

“But then they add ‘if you can do it, it’s going to be awesome.’”