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Increasing evidence suggests that the highly complex and dynamic environment of bacterial and human cells imposes critical control on cellular functions which are difficult to mimic under in vitro conditions. Complementary to high-resolution light microscopy and electron tomography, in-cell solution-state NMR can track such structural and dynamical interactions at the most detailed, i.e., atomic level, provided that the molecular units tumble rapidly. Cellular solid-state NMR (ssNMR), on the other hand, provides increasing possibilities to probe molecular structure in bacterial and human cell preparations largely irrespective of molecular size. Here we review preparative as well as methodological aspects of such studies and highlight recent applications focusing on proteins embedded in their natural cell membrane environment.

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