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Updated: Nov 3, 2025
Folding and Characterization of a Bio-responsive Robot from DNA Origami
Published on: December 3, 2015
Tight nanoscale clustering of Fcγ receptors using DNA origami promotes phagocytosis
Nadja Kern1,2, Rui Dong1,2, Shawn M Douglas1
1Department of Cellular and Molecular Pharmacology, University of California San Francisco, San Francisco, United States.
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.
Insights
Macrophages decide to engulf antibody-coated targets based on how tightly clustered the antibody ligands are. Closer ligand spacing significantly improves the efficiency of this crucial cellular process.
Area of Science:
- Immunology
- Cell Biology
- Nanotechnology
Background:
- Macrophages employ Fc gamma receptors (FcγRs) for phagocytosis of antibody-opsonized targets, a critical immune defense mechanism.
- The precise molecular mechanisms governing the activation threshold for FcγR-mediated phagocytosis remain incompletely understood.
Purpose of the Study:
- To investigate how the nanoscale organization of ligands influences FcγR-driven phagocytosis by macrophages.
- To elucidate the role of ligand spacing and clustering in initiating the phagocytic response.
Main Methods:
- Development of a DNA origami-based system for precise control over ligand number and spacing on target surfaces.
- Quantitative analysis of macrophage engulfment efficiency under varying ligand densities and spacings.
- Measurement of FcγR phosphorylation and downstream signaling events.
Main Results:
- Reducing ligand spacing from 17.5 nm to 7 nm significantly enhanced macrophage engulfment, even with a constant ligand number.
- Enhanced engulfment was primarily attributed to improved efficiency in the initiation phase of phagocytosis.
- Tighter ligand clustering led to increased FcγR phosphorylation and proximal signaling, but not simply by recruiting more signaling domains to individual complexes.
Conclusions:
- Macrophages integrate information about local ligand density, not just ligand number, to regulate phagocytosis.
- Receptor clustering, driven by reduced ligand spacing, is essential for overcoming the phagocytic threshold.
- Findings provide insights into antibody-mediated phagocytosis and inform the design of targeted immunotherapies.
