ABSTRACT
T-cell activation by dendritic cells (DCs) depends on pushing and pulling forces exerted by the T-cell actin cytoskeleton. This process is enhanced by a series of changes in the DC, collectively termed maturation. Using atomic force microscopy, we show that during maturation, DC cortical stiffness is increased via a process that depends on actin polymerization. By manipulating the stiffness of T-cell substrates using stimulatory hydrogels or DCs expressing mutant cytoskeletal proteins, we show that increasing stiffness over the range observed during DC maturation enhances T-cell activation. Stiffness sensitivity is conserved in CD4+ and CD8+ T-cells, in both naïve and effector populations. Since increased stiffness lowers the agonist dose needed to activate naïve T cells, we conclude that mechanical cues function as co-stimulatory signals. Taken together, our data reveal that maturation-associated changes in the DC cytoskeleton alter its biophysical properties, creating a platform for enhanced mechanotransduction in interacting T-cells