Masullo, L. A. et al. Nat. Commun. 9, 3281 (2018).

Super-resolution microscopy is often considered challenging to apply to living specimens because of the high, potentially toxic light doses and long collection times typically used to generate images. Masullo et al. addressed this challenge by developing the ‘molecular nanoscale live imaging with sectioning ability’ (MoNaLISA) nanoscope for prolonged super-resolution imaging with relatively low light intensities. MoNaLISA is conceptually similar to reversible saturable optical fluorescent transition (RESOLFT) microscopy, but it overcomes the limitations of that approach by using light patterns with optimized shapes and periodicities to control the reversibly switchable fluorescent proteins used for labeling. The result is a microscopy method that achieves ~50-nm resolution over entire cell volumes over long periods. The researchers demonstrated the approach for time-lapse imaging of organelles, colonies of mouse embryonic stem cells, and neurons.