Chemokine-induced cell swelling fluidises the plasma membrane to regulate CD8+ T cell migration

T cell migration is primarily viewed as a cytoskeletal process. Here, we show that chemokine-stimulated CD8+ T cell migration is modulated by a volume-driven biophysical switch at the plasma membrane (PM). We found that chemokine-induced cell swelling creates an adhesion-dependent gradient of high PM fluidity at the leading edge. External chemical fluidisation of the PM using membrane modulators enhances migration similar to chemokine-induced fluidisation without the need of cell-swelling. Together, our findings identify PM fluidity as a tuneable biophysical gatekeeper that controls T cell migration, potentially providing a novel mechanical tool for optimising adoptive cell therapies in restrictive tissue microenvironments.