In a new study, researchers at the Indian Institute of Science (IISc) show how epithelial tissues exhibit slow-moving glass-like behaviour despite their fast-paced biological activity, resolving a long-standing mystery.
Such behaviour is important for maintaining coordinated cellular response and has implications for biological processes ranging from wound healing to disease progression. The team also shows that this behaviour is shaped by a combination of a cell's biochemical activity and the mechanical forces it experiences from its neighbours.
Glasses behave like solids while retaining the disordered structure of liquids. Similar behaviour has been observed in epithelial tissues, the sheets of cells that line organs and body surfaces. These tissues have regions where cells become trapped and move extremely slowly, co-existing right next to zones where cells move fast. This phenomenon, known as dynamic heterogeneity, is a hallmark of glass-like behaviour .
Theoretical models so far suggest that tissues undergo dynamic arrest or glass-like behaviour only when cellular activity is very low, and cell density is extremely high – when the system is passive. But in active tissues, continuous cellular activity should promote tissue fluidisation (a state where cells move past one another easily). Epithelial tissues, however, present a mystery, as they are metabolically active yet behave mechanically like glass.
To delve deeper, the team combined time-lapse microscopy imaging with theoretical and computational modeling. Using epithelial cell monolayers fluorescently tagged for actin – a key component that controls cell shape and movement – the researchers tracked both cell movement and biochemical organisation over time. They also quantified cellular forces using Traction Force microscopy and mapped spatial actin organisation.
“The first result that I got showed oscillation of actin levels over time,” remembers Sindhu Muthukrishnan, PhD student at the Department of Bioengineering and first author. These levels, which reflect cellular activity, oscillated over an hour – much slower than the minute-scale oscillations typically seen in isolated cells. “I spent a lot of time trying to understand where this hour-scale oscillation in actin is coming from,” she adds. What the team eventually realised was that in epithelial tissues, packed cells are mechanically influencing one another, pointing to a link between cellular mechanics, actin organisation, and collective tissue behaviour.
To explain these observations, the researchers tested several existing theoretical models, including the widely used vertex model, to mimic collective behaviour of epithelial tissue. However, these models could not reproduce the experimentally observed glass-like dynamics. For active epithelial tissues, simulations consistently predicted tissue fluidisation.
The researchers therefore developed an active vertex model that incorporated mechanochemical feedback – the continuous two-way interaction between cellular biochemistry and the mechanical forces between cells. “The mechanochemical feedback loop provides a new way of looking at things,” says Phanindra Dewan, PhD student at the Department of Physics and one of the authors. The new simulations successfully reproduced experimental signatures of glass dynamics and revealed that mechanochemical feedback, together with cellular crowding, is essential for the emergence of glass-like behaviour in epithelial tissues.
“Such feedback could explain similar behaviour in other tissues too,” says Medhavi Vishwakarma, Assistant Professor at the Department of Bioengineering and one of the corresponding authors. “In other tissues, similar pathways may lead to other interesting features; in fact, many of these pathways are still not explored fully,” she explains.
The study also opens new avenues in bioengineering research by providing a different look at how complex biological systems are studied. “The study of cancer progression or disease emergence or embryonic development is not just a question about genetics or biochemistry but also a question about mechanics,” explains Sumantra Sarkar, Assistant Professor at the Department of Physics and one of the corresponding authors.
Nature Communications
Glassy dynamics in active epithelia emerge from an interplay of mechanochemical feedback and crowding
10-Jun-2026