Epithelial cells in developing embryos and healing wounds synchronize and collectively pulse as they migrate, according to MIT researchers publishing in the journal Newton. In a finding that could serve as an early warning sign for cancer metastasis, malignant epithelial cells demonstrated twice the rhythmic persistence of healthy cells.
Decoding the Cellular Rhythm of Epithelial Sheets
Epithelial cells act as the foundational protective barriers lining the human body. They form the outer layers of skin, wrap around internal organs, and line blood vessels. During embryogenesis, these cells divide, migrate, and organize to construct tissue architectures. When tissue suffers damage from a physical scrape, an internal tear, or a surgical incision, epithelial cells mobilize, migrating directly to the injury site to close the wound.
Scientists mapped these migrations mainly through spatial coordination—tracking where cells moved relative to one another and where they eventually settled in growing tissues. Temporal coordination, or how cellular movement relates over time, was less well-understood.
Wenhui Tang, a former MIT graduate student who completed her SM in 2020 and PhD in 2024, noticed a repeating temporal pattern while studying collective cell migration. As documented in the Newton study, cells were observed swelling, crowding together, and then spreading apart in repeated cycles. The team realized these localized patterns represented a synchronized rhythm operating across cellular sheets.
Microscopy and Methodology Behind the Discovery
To capture this rhythmic pulsing, the MIT researchers cultured healthy live epithelial cells in laboratory dishes, adding fluorescent dyes to illuminate individual cell nuclei. Maintaining the cells in nutrient-rich media allowed them to undergo natural growth, division, and migration phases.
Using confocal microscopy, the team recorded snapshots every few minutes over periods lasting up to 30 hours. When assembled into sequential time-lapse movies, the footage revealed distinct mechanical waves rippling across the cell sheets. Ten hours of MDCK kidney cells forming tightly packed sheets clearly demonstrated individual green nuclei repeatedly crowding together and dispersing.
Alongside first author Wenhui Tang and Ming Guo, professor of mechanical engineering at MIT, the research team included Mehrana Nejad and L. Mahadevan from Harvard University, alongside Adrian Pegoraro from the Metrology Research Centre of the National Research Council Canada.
Malignant Cells Exhibit Prolonged Synchronization
The research team expanded their observations beyond healthy tissue, measuring collective rhythmic pulsing across multiple epithelial phenotypes. They analyzed healthy cells alongside cells derived from benign tumors and cancerous cells.
The comparative analysis revealed a behavioral divergence in temporal persistence. Malignant epithelial cells maintained their synchronized pulsing for twice as long as healthy cells, displaying a steadier and more persistent rhythm throughout their migration.
“More aggressive cancer cells tend to have a steadier and more persistent rhythm as compared to healthy ones,” states Ming Guo, professor of mechanical engineering at MIT, highlighting the predictive potential of these mechanical dynamics. “We think this coordination could serve as an early warning sign of how likely a tumor is to spread. The same coordinated waves may help shape embryos during development and close wounds upon injury.”
While it is unclear why the cells sync up in this way, the stability of the rhythmic pulsing provides a mechanical signature.
