In-cell NMR: recent progresses and future challenges

In-cell NMR, i.e., NMR spectroscopy applied to studying specific macromolecules within living cells, is becoming the technique of choice for the structural and mechanistic description of proteins and nucleic acids within increasingly complex cellular environments, as well as of the temporal evolution of biological systems over a broad range of timescales. Furthermore, in-cell NMR has already shown its potentialities in the early steps of drug development. In this Perspective, we report some of the most recent methodological advancements and successful applications of in-cell NMR spectroscopy, focusing particularly on soluble proteins. We show how the combination of the atomic-level characterization of NMR with its application to a cellular context can provide crucial insights on cellular processes and drug efficacy with unprecedented level of detail. Finally, we discuss the main challenges to overcome and share our vision of the future developments of in-cell NMR and the applications that will be made possible.