Matrix Viscoelasticity Regulates Dendritic Cell Migration and Immune Priming

The tumor microenvironment shapes immune surveillance through its mechanical properties, yet the role of matrix viscoelasticity remains unclear. Here, we used a tunable collagen system that models human tissue viscoelasticity to define how matrix relaxation directs dendritic cell (DC) behavior. Slow-relaxing, elastic networks restrict actomyosin-driven remodeling, limiting DC motility and reducing DC-T cell encounters and activation. Blocking DC migration in fast-relaxing matrices recapitulated key aspects of the impaired T cell priming seen in elastic networks, identifying migration as a mechanical checkpoint for immune activation. Prolonged confinement in elastic matrices induced a mechanomemory state, locking DCs into a state of reduced motility and altered chromatin accessibility. Studies using patient-derived ependymoma samples confirmed these findings, establishing viscoelastic relaxation as a key physical regulator of immune priming. Together, this tunable viscoelastic platform provides a defined, human-relevant model to dissect and model mechanical control of immunity for therapeutic design.