Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
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...
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doaj-22326acb213c44e0bb2e15c5800764e02021-06-07T14:28:27ZengeLife Sciences Publications LtdeLife2050-084X2021-06-011010.7554/eLife.68311Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosisNadja Kern0https://orcid.org/0000-0002-1313-5890Rui Dong1https://orcid.org/0000-0002-9118-3636Shawn M Douglas2https://orcid.org/0000-0001-5398-9041Ronald D Vale3https://orcid.org/0000-0003-3460-2758Meghan A Morrissey4https://orcid.org/0000-0002-0531-4864Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California San Francisco, San Francisco, United StatesDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California San Francisco, San Francisco, United StatesDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, United StatesDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, United States; Howard Hughes Medical Institute, University of California San Francisco, San Francisco, United States; Howard Hughes Medical Institute Janelia Research Campus, Ashburn, United StatesDepartment of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, United States; Department of Molecular, Cellular and Developmental Biology, University of California Santa Barbara, Santa Barbara, United StatesMacrophages 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.https://elifesciences.org/articles/68311PhagocytosisAntibodyDNA origamiimmunotherapyFc Receptorsynthetic biology |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nadja Kern Rui Dong Shawn M Douglas Ronald D Vale Meghan A Morrissey |
spellingShingle |
Nadja Kern Rui Dong Shawn M Douglas Ronald D Vale Meghan A Morrissey Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis eLife Phagocytosis Antibody DNA origami immunotherapy Fc Receptor synthetic biology |
author_facet |
Nadja Kern Rui Dong Shawn M Douglas Ronald D Vale Meghan A Morrissey |
author_sort |
Nadja Kern |
title |
Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis |
title_short |
Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis |
title_full |
Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis |
title_fullStr |
Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis |
title_full_unstemmed |
Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis |
title_sort |
tight nanoscale clustering of fcγ receptors using dna origami promotes phagocytosis |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2021-06-01 |
description |
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. |
topic |
Phagocytosis Antibody DNA origami immunotherapy Fc Receptor synthetic biology |
url |
https://elifesciences.org/articles/68311 |
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