Journal
APL BIOENGINEERING
Volume 3, Issue 1, Pages -Publisher
AIP Publishing
DOI: 10.1063/1.5067301
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Funding
- National Institutes of Health (NIH), National Institute of Dental and Craniofacial Research (NIDCR), Office of Director [DP2DE023319]
- National Institute of Allergy and Infectious Disease [R21AI128519]
- UC Irvine (Institute for Clinical and Translational Sciences)
- Edwards Lifesciences Fund
- NIH National Heart, Lung, and Blood Institute T32 Training Grant in Cardiovascular Applied Research and Entrepreneurship [T32HL116270]
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Macrophages are versatile cells of the innate immune system that can adopt a variety of functional phenotypes depending on signals in their environment. In previous work, we found that culture of macrophages on fibrin, the provisional extracellular matrix protein, inhibits their inflammatory activation when compared to cells cultured on polystyrene surfaces. Here, we sought to investigate the role of matrix stiffness in the regulation of macrophage activity by manipulating the mechanical properties of fibrin. We utilize a photo-initiated crosslinking method to introduce dityrosine crosslinks to a fibrin gel and confirm an increase in gel stiffness through active microrheology. We observe that matrix crosslinking elicits distinct changes in macrophage morphology, integrin expression, migration, and inflammatory activation. Macrophages cultured on a stiffer substrate exhibit greater cell spreading and expression of alpha M integrin. Furthermore, macrophages cultured on crosslinked fibrin exhibit increased motility. Finally, culture of macrophages on photo-crosslinked fibrin enhances their inflammatory activation compared to unmodified fibrin, suggesting that matrix crosslinking regulates the functional activation of macrophages. These findings provide insight into how the physical properties of the extracellular matrix might control macrophage behavior during inflammation and wound healing. (C) 2019 Author(s).
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