Development of fusogenic glass surfaces that impart spatiotemporal control over macrophage fusion: Direct visualization of multinucleated giant cell formation.
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.
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA; Center for Metabolic and Vascular Biology, Mayo Clinic, Scottsdale, AZ 85259, USA.
James J
JJ
Faust
Department of Physics, Arizona State University, Tempe, AZ 85287, USA; Center for Biological Physics, Arizona State University, Tempe, AZ 85287, USA.
Wayne
W
Christenson
Department of Civil and Environmental Engineering and Earth Sciences, University of Notre Dame, Notre Dame, IN 46556, USA.
Kyle
K
Doudrick
Department of Physics, Arizona State University, Tempe, AZ 85287, USA; Center for Biological Physics, Arizona State University, Tempe, AZ 85287, USA.
Robert
R
Ros
School of Life Sciences, Arizona State University, Tempe, AZ 85287, USA; Center for Metabolic and Vascular Biology, Mayo Clinic, Scottsdale, AZ 85259, USA. Electronic address: Tatiana.Ugarova@asu.edu.
Tatiana P
TP
Ugarova
D000327:Adsorption; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002459:Cell Fusion; D015726:Giant Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D005898:Glass / Q000737:chemistry*; D057809:HEK293 Cells; D006801:Humans; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009829:Oleic Acids / Q000494:pharmacology; D055620:Optical Phenomena; D013499:Surface Properties; D013997:Time Factors
D016177:Macrophage-1 Antigen; D009829:Oleic Acids; C029407:oleylamide
Foreign body reaction; Live imaging; Mac-1 integrin; Macrophage fusion; Microscopy; Multinucleated giant cells