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Lipid Rafts Direct Macrophage Motility in the Tissue Microenvironment

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Abstract

Infiltrating leukocytes are exposed to a wide range of tissue elasticities. While we know the effects of substrate elasticity on acute inflammation via the study of neutrophil migration, we do not know its effects on leukocytes that direct chronic inflammatory events. Here, we studied morphology and motility of macrophages, the innate immune cells that orchestrate acute and chronic inflammation, on polyacrylamide hydrogels that mimicked a wide range of tissue elasticities. As expected, we found that macrophage spreading area increased as substrate elasticity increased. Unexpectedly, we found that morphology did not inversely correlate with motility. In fact, velocity of steady-state macrophages remained unaffected by substrate elasticity, while velocity of biologically stimulated macrophages was limited on stiff substrates. We also found that the lack of motility on stiff substrates was due to a lack of lipid rafts on the leading edge of the macrophages. This study implicates lipid rafts in the mechanosensory mechanism of innate immune cell infiltration.

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Acknowledgments

Thank you to Mason Hui and Norell Hadzimichalis for editing this manuscript. Funding was provided by the JFK Neuroscience Institute and the JFK Foundation.

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Authors declare no conflict of interest.

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Correspondence to Michelle L. Previtera.

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Associate Editor Jennifer West oversaw the review of this article.

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Previtera, M.L., Peterman, K., Shah, S. et al. Lipid Rafts Direct Macrophage Motility in the Tissue Microenvironment. Ann Biomed Eng 43, 896–905 (2015). https://doi.org/10.1007/s10439-014-1142-1

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  • DOI: https://doi.org/10.1007/s10439-014-1142-1

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