The shape of things to come: How spheroid geometry guides multicellular orbiting and invasion

"We saw that the cells were pulling a little harder in places where the original culture was a little bit sharper, where it deviates a little from being spherical," said Hyuntae Jeong, a postdoctoral researcher in Brown's School of Engineering and the study's second author. "One of the consequences of that pulling is that it starts to reshape the collagen that surrounds the cells, aligning the fibers radially and steering the cells outward."

The researchers further showed that they could alter the invasion pattern by changing the surrounding osmotic pressure - the ability of water to pass between the cell clusters and the external matrix. When "squeezed" under higher osmotic pressure, cells were arrested within the original spheroid and paused their invasion. Increasing pressure during the cell invasion phase caused lines of invading cells to retract back into the original spheroid, underscoring the importance of the physical environment on cell behavior.

The researchers hope the work might be a step toward understanding the complex dynamics of how tissues develop, as well as how cancer cells break free of tumors to spread around the body. There's much more work to be done, but unpacking how cells interact with each other and their surroundings could be key pieces of the puzzle.

"This is really an argument for understanding the cellular microenvironment," Wong said. "Cells are getting instructions from each other, but also from their surroundings. And they're able to reshape their surroundings in important ways. We think it's worth looking more deeply into these interactions between cells and their surroundings."

Co-authors of the research were Carles Falcó (University of Oxford), Alex M. Hruska (Brown), W. Duncan Martinson (Francis Crick Institute), Alejandro Marzoratti (Brown), Mauricio Araiza (University of Wisconsin, Madison), Haiqian Yang (MIT), Vera C. Fonseca (Brown), Stephen A. Adam (Northwestern), Christian Franck (Wisconsin), José A. Carrillo (Oxford) and Ming Guo (MIT). The work was primarily supported by Brown University's Hibbitt Engineering Fellowship, the National Institutes of Health (R01GM140108) and the U.S. Army Research Office (W911NF2310385).