ABSTRACT

It has long been a dream of cell biologists to catch a glimpse of the supramolecular architecture inside living cells, hitherto largely an uncharted territory. Vital cellular functions are performed by ensembles of macromolecules - or complexes - but many of them exist only transiently or are held together by forces too weak to withstand conventional biochemical isolation and purification procedures. The development of cryoelectron tomography has made it possible to obtain three-dimensional images of whole ice-embedded cells or organelles with resolutions in the range of 5 nm, and with advanced instrumentation we are now entering the realm of molecular resolution. This allows the visualisation of macromolecular complexes in an unperturbed functional environment. Such tomograms are essentially 3-D images of the cell's entire proteome, but exploitation of this imposing amount of information is confronted with technical problems. Sophisticated pattern recognition techniques are needed to retrieve the information about territorial distribution of macromolecules and their organization in functional neighborhoods, and thereby bridge the gap between molecular and cellular structural biology.