Modulation of macrophage phenotype by cell shape

Significance Macrophages are central regulators of the immune response during infection and wound healing, and their behavior is largely thought to be regulated by soluble factors in the microenvironment. Here, we find that adhesive cues are also critical for regulating the proinflammatory vs. prohealing state of these cells. We use engineered cell culture substrates to control cell shape and find that elongation of cells promotes a prohealing phenotype. Moreover, we identify key molecular pathways that are responsible for transducing physical cues to the biochemical cues that govern this response. Together, these studies suggest an important role for cell shape in regulating macrophage function.