T-cell activation is modulated by the 3D mechanical microenvironment

T cells recognize mechanical forces through a variety of cellular pathways, including mechanical triggering of both the T-cell receptor (TCR) and integrin LFA-1. Here we show that T cells can recognize forces arising from the mechanical rigidity of the microenvironment. We fabricated 3D scaffold matrices with mechanical stiffness tuned to the range 4–40 kPa and engineered them to be microporous, independently of stiffness. We cultured T cells and antigen presenting cells within the matrices and studied T-cell activation by flow cytometry and live-cell imaging. We found that there was an augmentation of T-cell activation, proliferation, and migration speed in the context of mechanically stiffer 3D matrices as compared to softer materials. These results show that T cells can sense their 3D mechanical environment and alter both their potential for activation and their effector responses in different mechanical environments. A 3D scaffold of tunable stiffness and consistent microporosity offers a biomaterial advancement for both translational applications and reductionist studies on the impact of tissue microenvironmental factors on cellular behavior.