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.