Looking at Proteins Inside Live Cells with Atomic Resolution: Science Fiction or Science Reality?
Ever since we realized that cells constitute the basic building blocks of all life, we thrive to develop tools to 'look inside them' to resolve the architectures and mechanisms that define their functions. Whilst 'looking into cells' is typically used in reference to methods in optical microscopy, high-resolution in-cell NMR spectroscopy offers exciting new possibilities for structural and functional studies in intact cells. In contrast to classical imaging techniques, in-cell NMR does not provide spatial information on intracellular biomolecules. Instead, it delineates atomic-resolution ensemble descriptions of cellular structures, including real-time snapshots of post-translational protein modification states. Because NMR is a non-invasive and non-destructive method, we record such snapshots over extended periods of time, and in a virtually continuous manner. We then assemble them as frames of a movie to visualize the structural and functional properties of proteins inside live cells.