T Cells Can Physically Sense Tissue Stiffness, McGill Study Finds

T cells are immune cells that help the body detect and destroy infections, cancerous cells, and other threats, and some go on to form long-lasting immune memory. A study led by McGill University in Canada has found that T cells can also physically sense how stiff the tissue around them is, an ability scientists did not previously know they had, and use this cue to help decide whether they become long-lived memory cells. The findings were published in the peer-reviewed journal Nature Immunology on July 3, 2026.

Scientists had assumed that tissue-resident memory T cells, immune cells that remain in tissues after an infection clears and react quickly if the same threat returns, are guided mainly by chemical signals. "This is an exciting fundamental finding that challenges the way we think about immune cells," said lead author Judith Mandl, a professor in McGill's Department of Physiology. "It suggests T cells can 'feel' their surroundings and adapt to them," she said, adding that this makes the physical environment an active force in shaping their behavior.

To test this, researchers placed immune cells from humans and mice into engineered collagen gels designed to mimic tissues of varying stiffness. Cells placed in stiffer gels were more likely to develop features resembling tissue-resident memory cells, which are linked to long-term immune protection.

The research involved McGill's Department of Physiology, the Alan Edwards Centre for Research on Pain, the Department of Bioengineering, the McGill University Health Centre, and collaborators in the Netherlands and the United States. The researchers say the finding could inform new approaches to autoimmune diseases, allergies, and transplant rejection, conditions in which T cells wrongly target healthy tissue, and may be relevant to cancer, since dense tumors are often physically difficult for immune cells to penetrate.

The researchers next want to identify the molecular sensor that allows T cells to detect tissue stiffness and convert that mechanical force into a biological response.