Macrophages are immune cells that gobble intruders, renegades and debris. Now researchers discover cell shape can help control macrophages — for instance, elongating them promotes behavior that enhances healing. These findings, detailed in the Proceedings of the National Academy of Sciences, could help develop better materials to encourage tissue repair.
Macrophages play a variety of roles — for instance, in their M1 state they promote inflammation, while in their M2 state they encourage healing. Which role macrophages play is largely thought to be controlled by chemical signals dissolved in their surroundings, but some recent studies hinted physical cues in their environment might influence their behavior as well.
Biomedical engineer Wendy Liu at the University of California, Irvine, and her colleagues noted there was evidence suggesting macrophages could adopt different shapes in the body. They sought to explore how these changes might influence their activity.
The scientists found when they stimulated macrophages with chemicals to make them adopt certain states, they exhibited dramatic changes in cell shape. Pro-healing M2 cells were elongated compared to pro-inflammation M1 cells.
The researchers then laid down stripes of the sugary protein fibronectin onto lab dishes and grew macrophages on them. The width and the spacing of the stripes helped control how elongated the macrophages became. They found elongation triggered changes toward the pro-healing M2 state. Elongation also enhanced the effect of chemicals that stimulated the M2 state if they were introduced and inhibited the effect of molecules that normally triggered the pro-inflammation M1 state.
When macrophages were dosed with chemicals that stifled how much their cytoskeletons — their internal scaffolds — could move, the researchers found this suppressed elongation-triggered changes toward the pro-healing M2 state. This suggests the cytoskeleton helps control shape-triggered changes in macrophage roles.
Macrophage shape is controlled in part by sticky interactions with the surrounding extracellular matrix. “There are dramatic changes in extracellular matrix architecture during wound healing as well as disease conditions such as cancer or atherosclerosis where macrophages are involved,” Liu notes.
These results not only help shed light on the fundamental behavior of macrophages, but they could also have important implications in developing therapies for tissue healing and regeneration.
“Currently, we are developing biomaterial surfaces that encourage changes in macrophage shape to promote wound healing,” Liu says. “Such materials may be useful for implanted devices or tissue-engineered constructs.”