Open Access
Open access
eLife, volume 10

Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis

Publication typeJournal Article
Publication date2021-06-03
Journal: eLife
scimago Q1
SJR3.932
CiteScore12.9
Impact factor6.4
ISSN2050084X
PubMed ID:  34080973
General Biochemistry, Genetics and Molecular Biology
General Medicine
General Immunology and Microbiology
General Neuroscience
Abstract

Macrophages destroy pathogens and diseased cells through Fcγ receptor (FcγR)-driven phagocytosis of antibody-opsonized targets. Phagocytosis requires activation of multiple FcγRs, but the mechanism controlling the threshold for response is unclear. We developed a DNA origami-based engulfment system that allows precise nanoscale control of the number and spacing of ligands. When the number of ligands remains constant, reducing ligand spacing from 17.5 nm to 7 nm potently enhances engulfment, primarily by increasing efficiency of the engulfment-initiation process. Tighter ligand clustering increases receptor phosphorylation, as well as proximal downstream signals. Increasing the number of signaling domains recruited to a single ligand-receptor complex was not sufficient to recapitulate this effect, indicating that clustering of multiple receptors is required. Our results suggest that macrophages use information about local ligand densities to make critical engulfment decisions, which has implications for the mechanism of antibody-mediated phagocytosis and the design of immunotherapies.

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