Wei, L. et al. Proc. Natl. Acad. Sci. USA 110, 11226–11231 (2013).

A cell's proteome is highly dynamic in nature, reflecting the cell cycle and surrounding environment. Newly synthesized proteins can be visualized in the cell using fluorescence-based methods, but such approaches generally require fixation. Imaging mass spectrometry–based methods, though powerful, require destruction of the cell. Wei et al. now apply stimulated Raman scattering (SRS) microscopy to image nascent proteins in live mammalian cells without fixation or staining. The method is simple and results in minimal cell perturbation: nascent proteins incorporate deuterium-labeled leucine, which, based on its unique vibrational signature, can be readily detected by SRS microscopy. Application of the method highlighted rapid protein turnover in nucleoli (the sites of ribosome biogenesis) and in neurites of neuron-like cells during differentiation.