Molecular cryo-electron tomography of vitreous tissue sections: current challenges.
Electron tomography of vitreous tissue sections (tissue TOVIS) allows the study of the three-dimensional structure of molecular complexes in a near-native cellular context. Its usage is, however, limited by an unfortunate combination of noisy and incomplete data, by a technically demanding sample preparation procedure, and by a disposition for specimen degradation during data collection. Here we outline some major challenges as experienced from the application of TOVIS to human skin. We further consider a number of practical measures as well as theoretical approaches for its future development.
Norlén
L
L
Department of Cell and Molecular Biology (CMB), Medical Nobel Institute, Karolinska Institute, Stockholm, Sweden. lars.norlen@ki.se
Oktem
O
O
Skoglund
U
U
D020285:Cryoelectron Microscopy / Q000379:methods*; D055032:Electron Microscope Tomography / Q000379:methods*; D006801:Humans; D021621:Imaging, Three-Dimensional; D012867:Skin / Q000648:ultrastructure