2023.06.26 Tuning T cell traits and functions with biomechanical materials

Tuning T cell traits and functions with biomechanical materials Generation of functionally distinct T-cell populations by altering the viscoelasticity of their extracellular matrix | Nature Biomedical Engineering Mechanical T cell stimulation: T cells for adoptive T cell therapies can be mechanically stimulated in tunable ECM-mimicking hydrogels to become effector-like or memory-like, depending on the viscoelasticity of hydrogel. More viscous hydrogels whose embedded collagen fibers (blue) were only weakly cross-linked with a synthetic cross-linker molecule (red) resulted in memory-like T cells (left), whereas more elastic hydrogels with strongly crosslinked collagen fibers resulted in effector-like T cells. cryoEM of ECM-mimicking hydrogel: This cryoEM image shows an ECM-mimicking hydrogel with room for T cells to pass through and attach to the specifically engineered collagen matrix. Credit: Wyss Institute at Harvard University Mechanical stimulation schematic: This illustration shows a comparison of T cells that, on the top, are exposed to a less elastic, more viscous hydrogel, and, on the bottom, to a more elastic, less viscous hydrogel. Stimulation with a more elastic hydrogel induces them to differentiate into effector-like T cells that have greater potential to kill tumor cells than memory-like T cells resulting from stimulation with a less elastic hydrogel. Credit: Wyss Institute at Harvard University