Matrix Viscoelasticity Regulates Dendritic Cell Migration and Immune Priming

Area of Science:

• Biophysics
• Immunology
• Cancer Biology

Background:

• The tumor microenvironment's mechanical properties influence immune surveillance.
• The specific role of matrix viscoelasticity in regulating immune cell behavior is not well understood.

Purpose of the Study:

• To investigate how matrix viscoelasticity and relaxation affect dendritic cell (DC) behavior and immune priming.
• To establish a tunable collagen system modeling human tissue viscoelasticity for studying immune cell mechanics.

Main Methods:

• Utilized a tunable collagen system to mimic human tissue viscoelasticity.
• Assessed dendritic cell (DC) motility, T cell interactions, and activation in matrices with varying relaxation properties.
• Investigated the effects of prolonged confinement and DC migration blockade.

Main Results:

• Slow-relaxing, elastic matrices restricted DC actomyosin remodeling, reducing DC motility and subsequent T cell encounters and activation.
• Blocking DC migration in fast-relaxing matrices mimicked impaired T cell priming observed in elastic networks.
• Prolonged DC confinement in elastic matrices induced a mechanomemory state, characterized by reduced motility and altered chromatin accessibility.
• Findings were validated in patient-derived ependymoma samples.

Conclusions:

• Viscoelastic relaxation is a critical physical regulator of immune priming within the tumor microenvironment.
• DC migration acts as a mechanical checkpoint for immune activation.
• The developed tunable viscoelastic platform offers a human-relevant model for dissecting mechanical control of immunity and informing therapeutic strategies.