Fig. 6. Stiffness-dependent modulation of Piezo1 activity modulates macrophage activation.

Activation of Piezo1 by IFNγ/LPS on stiff substrates promotes actin polymerization, which enhances channel mediated Ca²⁺ influx. Positive regulation between actin and Piezo1 enhances inflammation through activation of the transcription factor, NFκB and upregulation of inflammatory markers, including iNOS, TNFα and IL6. Ca²⁺ influx through Piezo1 channels on stiff substrates inhibits the activation of the transcription factor STAT6 and expression of healing markers, such as ARG1. Other stiffness mediated and Piezo1 independent mechanisms likely upregulate STAT6 activation in vitro.