Addressing cellular compartmentalization by in situ cryo-electron tomography

Atomic resolution structures have provided us with fascinating views and insights into the molecular architecture of many cellular components. At the same time, we have not exploited information on the interaction of these molecular players within their native environment, because conventional high resolution techniques demand fractionation and purification of cellular constituents. In situ cryo-electron tomography is about to change that. Significant advances in hardware instrumentation and sample preparation now reveal the cellular landscape in exquisite detail and at molecular resolution. We here review the technological developments that have enabled this highly visual approach, taking count of cellular constituents within close-to-life preparations.