Forces are everywhere, even within and between your cells. Cell forces are critical for wound healing, cancer progression, embryonic development, and the barrier function of tissues. But measuring these tiny forces can be tough. ASCB member Gaudenz Danuser, a professor at the University of Texas Southwestern Medical Center, and Mei Rosa Ng, now a research fellow at Massachusetts General Hospital, and their colleagues, developed an approach to measure forces on cell junctions between clusters of cells at subcellular scale. Their method was published in eLife in December.
“We wanted to develop an approach that would allow us to measure forces at a subcellular scale,” Danuser said. “People have been measuring [forces in cell] sheets, we wanted to understand the spatial organization of force exchange,” he added. To get at it, the researchers used a technique called thin-plate modeling coupled with high-resolution imaging.
Danuser explained, “We put a cluster of cells on a rubber substrate. Then we can measure with [fluorescent] beads how much the rubber deforms under the impact of the cells. There are other labs that have used this technique, but we are the first to do it with subcellular resolution.”
Danuser said that the key principle is Newton’s third law of motion that for every force in action, there is an equal and opposite reaction. “So if you see forces on the outside, they have to be the same on the inside. The thin plate model essentially creates a mirror image on the inside, and says what the force execution to has to be so that you can get that mirror image.” Danuser explained. A MATLAB algorithm ultimately calculates the forces based on imaging of the beads, and shows the tiny force vectors at the cell junctions (shown in the accompanying image).
Danuser continued, “I studied cell migration as a postdoc. Since then my labs have been studying mechanical control of migration and forces.” Danuser, who recently moved his lab from Harvard University to the University of Texas Southwestern Medical Center’s Cancer Prevention Institute of Texas, has plans for his force measuring technique. “I’m building a lab for cell survival and migration in tumors and metastatic secondary tumors… I think cell-cell interactions are incredibly important. With the tools we have now we have the ability to look at how forces are exchanged between cells, and we have biosensors to show signaling activities to look for domino effects and so forth in small tumor models. That’s what we’re gearing up for,” he said.
About the Author:
Christina Szalinski is a science writer with a PhD in Cell Biology from the University of Pittsburgh.