RT Journal Article
SR Electronic
T1 Tight nanoscale clustering of Fcγ-receptors using DNA origami promotes phagocytosis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.03.18.436011
DO 10.1101/2021.03.18.436011
A1 Nadja Kern
A1 Rui Dong
A1 Shawn M. Douglas
A1 Ronald D. Vale
A1 Meghan A. Morrissey
YR 2021
UL http://biorxiv.org/content/early/2021/03/18/2021.03.18.436011.abstract
AB 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.Competing Interest StatementThe authors have declared no competing interest.