Macrophage Mechanosensitivity Drives SIRPα Signaling

Students

2017
Engineering and Applied Sciences

Faculty

Professor of Chemical & Biomolecular Engineering

Project Summary

Macrophages are a type of white blood cell that play a crucial role in the immune system, responding to infections and engulfing target cells. The primary function of macrophages is to destroy foreign material and dead cells via phagocytosis, a process that is regulated by surface proteins on macrophages and their target cells. More specifically, the CD47-SIRPα pathway is known to inhibit phagocytosis. Macrophages have been studied extensively in the context of biochemical signaling via cytokines and chemokines, but it is likely that mechanical factors such as stiffness also play a role in regulating cell phenotype and behavior. The goal of my project was to determine how macrophage SIRPα signaling is regulated by tissue stiffness. I used fluorescence recovery after photobleaching (FRAP) to study SIRPα membrane motility and immunofluorescence microscopy to examine protein expression. One of the key findings was that THP-1 derived macrophages cultured on stiff collagen hydrogels exhibit a twofold increase in SIRPα expression as compared to macrophages cultured on soft hydrogels. Some of the results of this project were published in Current Biology. This finding may motivate further studies at the intersection of biophysics and cancer immunology, as tumor-associated macrophages play a key role in immunotherapy resistance pathways. 

This experience taught me valuable mechanobiology laboratory techniques such as hydrogel manufacture and immunostaining. Additionally, I learned how to form hypotheses about an experiment and plan follow-up experiments after obtaining initial results. I had the chance to work with specialists across fields such as chemical engineering, medical engineering, pharmacology, and physics, exposing me to interdisciplinary research. I am grateful that the Vagelos Undergraduate Research Grant allowed me to participate in this research.