Advancing formaldehyde cross-linking towards quantitative proteomic applications.

Formaldehyde is a key fixation reagent. This review explores its application in combination with qualitative and quantitative mass spectrometry (MS). Formalin-fixed and paraffin-embedded (FFPE) tissues form a large reservoir of biologically valuable samples and their investigation by MS has only recently started. Furthermore, formaldehyde can be used to stabilise protein-protein interactions in living cells. Because formaldehyde is able to modify proteins, performing MS analysis on these samples can pose a challenge. Here we discuss the chemistry of formaldehyde cross-linking, describe the problems of and progress in these two applications and their common aspects, and evaluate the potential of these methods for the future.