Two-photon-enabled near-infrared proximity labeling maps protein neighborhoods in vivo
Year: 2026
Type: preprint
Abstract: Native molecular neighborhoods govern biological processes and disease, yet existing approaches trade off penetration, precision, and native compatibility. Photocatalytic proximity labeling (PL) offers nanoscale, genetics-free precision but is limited by visible-light activation in optically opaque tissue. Here, we report 2PMap, a two-photon near-infrared PL platform driven by a sensitizer with a twophoton absorption cross-section nearly two orders of magnitude above conventional photocatalysts, enabling 850 nm continuous-wave excitation without pulsed lasers. In optically opaque samples, 2PMap achieved higher proteome coverage than conventional visible-light PL. In an early-stage Alzheimer’s disease mouse model, peptide-guided 2PMap produced the first proximity scale map of connective tissue growth factor (CTGF) in living brain tissue, capturing an 80-node network spanning extracellular-matrix, vascular, immune, and neuronal components within a microenvironment inaccessible to existing PL methods. 2PMap thus provides a genetics-free, modular platform for spatial proteomic mapping, extending molecular cartography to previously inaccessible living systems.
Source: ChemRxiv
Language: English
Topic: Biotin and Related Studies
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7223093502