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Watching Cancer Cells Play Ball

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Credit: Ning Wang, University of Illinois at Urbana-Champaign

As tumor cells divide and grow, they push, pull, and squeeze one another. While scientists have suspected those mechanical stresses may play important roles in cancer, it’s been tough to figure out how. That’s in large part because there hadn’t been a good way to measure those forces within a tissue. Now, there is.

As described in Nature Communications, an NIH-funded research team has developed a technique for measuring those subtle mechanical forces in cancer and also during development [1]. Their ingenious approach is called the elastic round microgel (ERMG) method. It relies on round elastic microspheres—similar to miniature basketballs, only filled with fluorescent nanoparticles in place of air. In the time-lapse video above, you see growing and dividing melanoma cancer cells as they squeeze and spin one of those cell-sized “balls” over the course of 24 hours.

The researchers, led by Ning Wang, University of Illinois at Urbana-Champaign, can create those tiny round microgels uniformly in various sizes using a droplet-based microfluidic device. For the outer layer, they’ve used alginate, an ingredient found in the cell walls of brown algae. That alginate polymer is ideal because mammalian cells can’t break it down. It’s also fully biocompatible. Mammalian cells grown in contact with the microspheres continue to divide as if nothing is amiss.

So, how do these inert microscopic spheres enable scientists to measure forces within living tissue? That’s where the fluorescent nanoparticles come in. As cells squish and squash the microspheres, they jostle the fluorescent nanoparticles inside them. All the jostling of those glowing nanoparticles is easily observed in real time using standard fluorescent light microscopy. Because the researchers know the microspheres’ precise physical properties, they’re able to use those images to calculate the 3D forces—including compression, tension, and shear—exerted by the cells on the balls’ surfaces.

The researchers have already begun to put their ERMG method to work and made some interesting observations. For instance, when melanoma cells taken from a mouse reproduce in a lab dish, growing from a single cell up to hundreds of cells, the average compressive stresses don’t increase. But within cancer tissue, the forces appear to be quite variable over time and space, suggesting that the mechanical stress on cancer cells vary in important ways that aren’t yet well understood.

The researchers have also used these microspheres in zebrafish to capture the natural mechanical forces that occur as an organism develops. Ultimately, they hope labs around world will embrace their new method to gain a deeper understanding of the cellular forces at work in our bodies. That might not be as exciting as watching the NBA’s Steph Curry play ball, but these images could contribute a lot to our understanding of this important aspect of biology.

References:

[1] Quantifying compressive forces between living cell layers and within tissues using elastic round microgels. Mohagheghian E, Luo J, Chen J, Chaudhary G, Chen J, Sun J, Ewoldt RH, Wang N. Nat Commun. 2018 May 14;9(1):1878. doi: 10.1038/s41467-018-04245-1.

Links:

Cancer Stat Facts: Melanoma of the Skin (National Cancer Institute/NIH)

Ning Wang (University of Illinois at Urbana-Champaign)

NIH Support: National Institute of General Medical Sciences