Syracuse University Magazine

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M. Lisa Manning



Modeling Tissue Formation

Scientists have long been challenged by the question of how embryonic tissue develops and organizes itself into organs and layers. For physics professor M. Lisa Manning of the College of Arts and Sciences and a team of scientists she works with, that question led to the creation of a mathematical model that allows them to study tissue development. Central to their work was whether embryonic tissue behaves more like a solid or a liquid—and why. “We found that embryonic tissue was viscoelastic—meaning that it behaved like a liquid, if you pushed on it slowly, but like a solid, if you pushed on it quickly,” says Manning, who received a prestigious CAREER Award from the National Science Foundation in January and was named a 2014 Sloan Foundation Research Fellow in Physics. “A mixture of cornstarch and water also behaves that way.”

Manning and the team, which includes biology and physics professor Eva-Maria Schoetz of the University of California, San Diego, and researchers Marcos Lanio and Jared Talbot of Lewis-Sigler Institute for Integrative Genomics at Princeton University, reported their findings in the journal Interface (Royal Society Publishing, 2013) in September. The work may have major implications for the study of tissue pattern formation and malformation.

The viscoelasticity, they learned, was the result of “glassy dynamics” in cells, caused by overcrowding. The research team discovered that cells within embryonic tissue were packed so tightly they rarely moved—and when they did so, they expended considerable energy to squeeze past their neighbors. Manning—an expert in theoretical soft condensed matter and biological physics who joined the SU faculty in 2011 following a postdoctoral fellowship at the Princeton Center for Theoretical Science—compares this behavior to riding on a subway. “If you’re on a subway train that’s not crowded, it’s easy to move toward the exit and get off the train,” she says. “But as more people get on the train, it takes longer to pick your way past them and exit. Sometimes, if the train is jam-packed, you miss your stop completely because you can’t move at all.”

Using state-of-the-art imaging and image analysis techniques, they saw that each cell was crowded by what Manning calls a “cage of neighbors.” A simple active-matter model, which they created, has enabled them to reproduce data and make predictions about how certain changes and mutations affect embryonic development. “This is exciting because if cells slow down or generate more sticky molecules, the tissue can turn into a solid,” says Manning, adding that such alterations can trigger malformations or congenital disease. “Our results provide a framework for understanding these changes.”

Manning’s work is rooted in that of another Princeton scientist, the late Malcolm Steinberg, who suggested more than 50 years ago that different types of embryonic tissue behave like immiscible liquids, such as oil and water. “This liquid-like behavior helps tissue separate into layers and form structures, including organs,” Manning says. “This type of work is fun because it involves knowledge from lots of disciplines, from soft-matter physics and materials science to cell and developmental biology.”  —Rob Enslin



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Professor M. Lisa Manning's research features experimental and simulation data in which two “droplets” of tissue join together, in a fluid-like manner, to form a single tissue.

Images courtesy of M. Lisa Manning