TY - JOUR
T1 - Development of fusogenic glass surfaces that impart spatiotemporal control over macrophage fusion
T2 - Direct visualization of multinucleated giant cell formation
AU - Faust, James J.
AU - Christenson, Wayne
AU - Doudrick, Kyle
AU - Ros, Robert
AU - Ugarova, Tatiana P.
N1 - Funding Information:
The authors wish to thank Mr. Tim Karcher for help with materials analysis. We also wish to thank Dr. Page Baluch for use of the EVOS FL Auto housed in the W.M. Keck Bioimaging Facility at ASU. The authors wish to thank members of the Ugarova Laboratory, and folks in the Center for Metabolic and Vascular Biology at Mayo Clinic for helpful discussion of this work. J.F. thanks the instructors at EMBL for teaching photoswitching photophysics (Dr. Mike Heilemann) and the technical aspects of GSDIM (Dr. Marko Lampe) and STED (Dr. Ulf Schwarz). This work was supported by NIH grant HL63199 to T.P.U.
Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Implantation of synthetic material, including vascular grafts, pacemakers, etc. results in the foreign body reaction and the formation of multinucleated giant cells (MGCs) at the exterior surface of the implant. Despite the long-standing premise that fusion of mononucleated macrophages results in the formation of MGCs, to date, no published study has shown fusion in context with living specimens. This is due to the fact that optical-quality glass, which is required for the majority of live imaging techniques, does not promote macrophage fusion. Consequently, the morphological changes that macrophages undergo during fusion as well as the mechanisms that govern this process remain ill-defined. In this study, we serendipitously identified a highly fusogenic glass surface and discovered that the capacity to promote fusion was due to oleamide contamination. When adsorbed on glass, oleamide and other molecules that contain long-chain hydrocarbons promoted high levels of macrophage fusion. Adhesion, an essential step for macrophage fusion, was apparently mediated by Mac-1 integrin (CD11b/CD18, αMβ2) as determined by single cell force spectroscopy and adhesion assays. Micropatterned glass further increased fusion and enabled a remarkable degree of spatiotemporal control over MGC formation. Using these surfaces, we reveal the kinetics that govern MGC formation in vitro. We anticipate that the spatiotemporal control afforded by these surfaces will expedite studies designed to identify the mechanism(s) of macrophage fusion and MGC formation with implication for the design of novel biomaterials.
AB - Implantation of synthetic material, including vascular grafts, pacemakers, etc. results in the foreign body reaction and the formation of multinucleated giant cells (MGCs) at the exterior surface of the implant. Despite the long-standing premise that fusion of mononucleated macrophages results in the formation of MGCs, to date, no published study has shown fusion in context with living specimens. This is due to the fact that optical-quality glass, which is required for the majority of live imaging techniques, does not promote macrophage fusion. Consequently, the morphological changes that macrophages undergo during fusion as well as the mechanisms that govern this process remain ill-defined. In this study, we serendipitously identified a highly fusogenic glass surface and discovered that the capacity to promote fusion was due to oleamide contamination. When adsorbed on glass, oleamide and other molecules that contain long-chain hydrocarbons promoted high levels of macrophage fusion. Adhesion, an essential step for macrophage fusion, was apparently mediated by Mac-1 integrin (CD11b/CD18, αMβ2) as determined by single cell force spectroscopy and adhesion assays. Micropatterned glass further increased fusion and enabled a remarkable degree of spatiotemporal control over MGC formation. Using these surfaces, we reveal the kinetics that govern MGC formation in vitro. We anticipate that the spatiotemporal control afforded by these surfaces will expedite studies designed to identify the mechanism(s) of macrophage fusion and MGC formation with implication for the design of novel biomaterials.
KW - Foreign body reaction
KW - Live imaging
KW - Mac-1 integrin
KW - Macrophage fusion
KW - Microscopy
KW - Multinucleated giant cells
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U2 - 10.1016/j.biomaterials.2017.02.031
DO - 10.1016/j.biomaterials.2017.02.031
M3 - Article
C2 - 28340410
AN - SCOPUS:85015635185
SN - 0142-9612
VL - 128
SP - 160
EP - 171
JO - Biomaterials
JF - Biomaterials
ER -