Laminin targeting of a peripheral nerve-highlighting peptide enables degenerated nerve visualization

Significance A fluorescently labeled nerve-binding peptide, NP41, holds promise to reduce surgical nerve damage and facilitate nerve repair. Clinical translation hinges on identification of binding targets to assess potential toxicity and understand the mechanism. For target identification, we developed a receptor capture method, enabling covalent tagging and identification of proteins within close proximity to a bound ligand. Extracellular matrix proteins laminin-421 and -211 were identified as NP41 binding targets, and TRICEPS-based glycoprotein capture supported laminin-421 as the primary binding target. This result explains the ability of NP41 to highlight degenerated nerve “ghosts” months after transection that were invisible to the unaided eye but contain laminins. Targeting extracellular matrix is advantageous for clinical imaging agents, likely reducing undesirable neurological effects.