Detecting Cellular Forces

The Physics of Biochemistry: A Fluorescence Based System for Seeing and Measuring Cellular Forces

Cells are constantly engaged in an interplay between biochemistry and mechanics by exerting forces and sensing the mechanical properties of their surroundings, says Assistant Professor of Chemistry Khalid Salaita, PhD, whose research focuses on new ways to visualize the biomechanical forces in living cells.

Salaita, whose work was recently featured in The Scientist magazine in an article titled, "Sensing a Little Tension," says that in our world, force can be measured with common tools, like the spring scale. But on a cellular or molecular level, it's a new game. Researchers are only just beginning to recognize the role that force plays in cell behavior and function, and starting to figure out how to measure it.

Nanoparticle (yellow) with polymer springs (gray) bound to a fluorophore and ligand (black). When a ligand binds to a receptor (purple), the spring “pulls” and the fluorophore elicits a signal (white).
Galipeau

Salaita's lab is one of the pioneering groups developing a force-sensing tool kit, and his team's approach involves a molecular spring. "It's very important that we understand forces and their role in cellular biology, but before we can do that, the first step that's needed is to measure the force. To find out the intensity (magnitude) and the location of where the forces are occurring. The method we’re developing allows us to do exactly that," he said, from his office in the Sanford Atwood Chemistry Center at Emory.

He uses a polymer "spring" (a polymer of antifreeze, just as a cool side fact) with organic fluorescent dye on one end and a quencher on the other. "We chemically modify the two ends of the polymer," he says. "One has a small protein that binds a receptor on the cell surface. The other end is anchored to a substrate." The tension-sensor is fluorescence-based so—and here's where it gets interesting—the more it is stretched, the brighter it glows.

It has long been known that cells touch, interact, and signal one another, says Clifford Michaels, Ph.D., intellectual property associate in the Office of Technology Transfer, but the tools have never existed to enable scientists to measure or observe those interactions. "Dr. Saliata's technology is an elegant solution for this challenging research problem, and will enable the field to move forward and answer questions they might not have been able to before," he says.  

Salaita never intended to build a molecular tension sensor. "We were measuring how receptors cluster on the cell surface. I gave a talk at the School of Medicine, and a student asked if we measured how receptors move vertically," he says. "It seemed that no one had a good way to do it."

His team chose the epidermal growth factor receptor so that it's biochemically important. "Its overexpression is related to many types of cancers," Salaita says. The real advance is that "we've developed a new technique to watch forces in a living cell in a time-lapse movie and the ability to quantify them," he says. "It's a technique anyone can use with a standard microscope. And we can use it on an unmodified cell, to measure mechanical forces that have never been measured before."

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