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

Abstract T cells recognize mechanical forces through a variety of cellular pathways, including mechanical triggering of the T-cell receptor (TCR) and mechanical triggering of the integrin LFA-1. We show here that T cells can recognize forces arising from the rigidity of the microenvironment. We fabricated 3D hydrogels with mechanical stiffness tuned to 4 kPa and 40 kPa and specially engineered be microporous independent of stiffness. We cultured T cells and antigen presenting cells within the matrices and studied activation by flow cytometry and live imaging. We found there was an augmentation of T-cell activation in the context of mechanically stiffer 3D material as compared to the softer material. In contrast, proliferation, activation markers, and migration were all diminished in T cells cultured in the softer material. These results show that T cells can sense their mechanical environment and amplify responses in the context of mechanical stiffness.