Bi, who spearheaded the study, says the group noticed how small changes in single cells, such as the number of adhesion molecules they expressed, could transform tissue from a solid-like jammed state to a fluid-like unjammed one. “Experts in the field had assumed that more adhesion led to a more solid-like state, but our model has predicted otherwise,” he says.
The model also states that an easy-to-measure number, quantifying cell shape, completely specifies the mechanical state of a tissue. "With no fit parameters, we predict that, if a tissue is solid-like, the cell-shape index should be 3.813; if the tissue is fluid-like, the number should be much larger than 3.813," Manning says. "That’s a very strong prediction, and no one has ever thought to look at it before.”
This prediction was put to the test in the Nature Materials article, titled "Unjamming and Cell Shape in the Asthmatic Airway Epithelium." Co-authored by Manning, Bi, and a team of researchers at the Harvard T.H. Chan School of Public Health, it focuses on cells from the lungs of human subjects, some of whom have asthma.
The team found that epithelial cells from the lungs of non-asthma patients quickly became solid-like, or jammed, as expected. “In people with asthma, the cells, however, scrambled around like there was a fire drill going on, and the tissue remained fluid-like for a much longer time,” Manning says. “We also found that, in the jammed tissues, the cell-shape index was precisely 3.813, while it was significantly larger in the unjammed tissues, as predicted by our theory. It was a spectacular confirmation.”
Now that Manning understands the impact of jamming transitions on disease, she says the next step is to measure and control these transitions in various medical conditions, such as asthma, cancer, and wound healing. “Our work suggests that the collective behavior of large groups of cells is easier to measure and is more important for disease than previously imagined," she says. "That means it's a very exciting time to be working in this field."