Tissue rigidity mechano-priming microglia cytoskeleton-nucleus interplays with biochemical signals to amplify neuroinflammatory responses

While the microenvironmental factors governing microglial activation are well understood, the impact of biophysical cues, such as tissue mechanics, remains largely unexplored. Here we examine the role of matrix rigidity in priming microglial activation, elucidating its interaction with biochemical signals to amplify neuroinflammatory responses.

Microglial cells mechanosensed the matrix rigidity by inducing progressive actin cytoskeleton development, morphological changes, and nuclear deformation. Notably, increased chromatin accessibility via histone acetylation was observed for genes associated with inflammation and mechanotransduction, suggesting a nuclear mechano-priming for microglial activation. The interplay between matrix rigidity and biochemical signals was facilitated through NF-κB signaling and cytoskeleton-mediated MRTF-A nuclear translocation.