Fibrinogen is readily functionalized with target proteins or ligands. (A) General three-step method to functionalize fibrinogen with a protein of interest using lysine reactivity. Reactive thiols are generated onto fibrinogen, which are then reacted with the maleimide-functionalized protein of interest (GFP, Con A, NeutrAvidin). Excess unreacted protein of interest is removed by differential native precipitation. (B) Two-step method to functionalize fibrinogen if the protein/ligand of interest has reactive thiols (for example, nanobodies engineered with cysteines). (C) One-step method to functionalize fibrinogen with an NHS derivative of a ligand of interest (biotin, fluorophores).