Light-mediated discovery of surfaceome nanoscale organization and intercellular receptor interaction networks
Proteomics
0301 basic medicine
Immunological Synapses
Light
Science
Antigen-Presenting Cells
Gene Expression
HL-60 Cells
Receptors, Cell Surface
Cell Communication
CD8-Positive T-Lymphocytes
Ligands
Lymphocyte Activation
Article
Antibodies
03 medical and health sciences
Cell Line, Tumor
Humans
Precision Medicine
B-Lymphocytes
Biological Products
Q
3. Good health
Optogenetics
Chromatography, Liquid
Protein Binding
DOI:
10.1038/s41467-021-27280-x
Publication Date:
2021-12-02T11:03:04Z
AUTHORS (21)
ABSTRACT
AbstractThe molecular nanoscale organization of the surfaceome is a fundamental regulator of cellular signaling in health and disease. Technologies for mapping the spatial relationships of cell surface receptors and their extracellular signaling synapses would unlock theranostic opportunities to target protein communities and the possibility to engineer extracellular signaling. Here, we develop an optoproteomic technology termed LUX-MS that enables the targeted elucidation of acute protein interactions on and in between living cells using light-controlled singlet oxygen generators (SOG). By using SOG-coupled antibodies, small molecule drugs, biologics and intact viral particles, we demonstrate the ability of LUX-MS to decode ligand receptor interactions across organisms and to discover surfaceome receptor nanoscale organization with direct implications for drug action. Furthermore, by coupling SOG to antigens we achieved light-controlled molecular mapping of intercellular signaling within functional immune synapses between antigen-presenting cells and CD8+ T cells providing insights into T cell activation with spatiotemporal specificity. LUX-MS based decoding of surfaceome signaling architectures thereby provides a molecular framework for the rational development of theranostic strategies.
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