T cells destroy cancer cells with force

As part of our immune defenses, cytotoxic T cells — or killer T cells — seek out and destroy infected or cancerous cells

These special immune cells are equipped with dissolved particles that contain two key components of immune attack: perforins (proteins that perfhole on target cells) and granulase (through which the cells enter and ultimately kill disease-causing cells

T cells snuggle up to the target lesion cell and form an intimate connection between the two called "cytotoxic immune synapses

The EMBL research team from the University of New South Wales' School of Biomedical Sciences at the University of New South Wales Sydney found that the mechanical forces produced by T cells affect the efficiency

The researchers detected physical forces within T cells that propelled the dissolved particles toward immune synapses, where their payloads are released

"This is a very exciting finding, in addition to mechanical tension and biochemical configuration, the shape of the target cell membrane plays an important role in T-cell-mediated cancer cell killing," said Dr Daryan Kempe, from the University of New South Wales' School of Medicine and Health, who co-led the

By stretching and bending the membrane of tumor cells in a specific direction, T cells make perforins easier to penetrate, but only if

Cell membranes that tend to bend outwards

Using the human melanoma cell line, the researchers demonstrated that perforins preferentially perforate tumor cell membranes that bend outwards rather than cell membranes that bend inwards

"When the particles arrive, their contents will be emptied

Measure the mechanical properties of cells

Maté Biro said most experiments rely on fine biophysical analysis

"This technique really allows us to tease out the whole integration process because it's a controlled approach

This study increases the understanding

T cell cytoskeletal forces shape synapse topography for targeted lysis via membrane curvature bias of perforin