Chemical cross-linking coupled to mass spectrometry was used to study the interaction between fibronectin (Fn; full-length or gelatin-binding domain fragment = Fn 45) with tissue transglutaminase 2 in oxidized and non-oxidized form. The complexes were cross-linked with disuccinimidyl suberate (DSS) or a combination of pimelic dihydrazide (PDH) in combination with the zero-length cross-linking reagent, DMTMM.