The “glue” holding your cells together has a surprising second job

A protein renowned for its role in connecting cells and tissues has been found to have an additional function. This protein, E-cadherin, assists epithelial cells—continuous layers throughout the body—in engulfing nearby dead cells. This discovery may impact understanding chronic inflammation. When dead cells decompose, they contribute significantly to inflammatory responses, and deciphering how tissues eliminate this material could uncover new insights into why the cleanup process may fail.

The study, published in Nature Communications, centers on the E-cadherin complex. This molecular system comprises E-cadherin along with three other proteins that bind epithelial cells lining various body areas such as skin, gut, and airways, providing the required structural integrity. In these tissues, each cell attaches to E-cadherin molecules on adjacent cells.

Researchers led by Verena Ruprecht studied epithelial tissues in living zebrafish and mouse embryos. They observed that the same molecular machinery also congregates at the site where a dying cell meets the tissue. To investigate further, they conducted two experiments. First, they exposed the tissue to dying cells devoid of E-cadherin.

The epithelial tissue removed these cells as effectively as it did normal dying cells. In the second experiment, fat droplets without any protein but carrying a signal typical on dying cells' surfaces were introduced. The epithelial cells engulfed these droplets as well.

Ruprecht, an ICREA Research Professor, expressed surprise at finding that epithelial cells repurpose their molecular adhesion machinery—the 'glue' usually holding them together—to engulf dying cells. Live imaging revealed that, despite the mechanical challenge of engulfing another cell's size, the upper and lower surfaces of the same epithelial cell can behave differently.

While the lower surface stretches and bends around the dead cell, the upper surface remains unchanged, preserving the tissue barrier. This behavior is similar to a row of dancers with linked arms, where their upper bodies remain steady while their feet execute increasingly complex movements when a dying cell appears.