MRC National Institute for Medical Research, London
Science for Health
3-D images of cell organelles
30 September 2009
A protein called von Willebrand Factor (VWF) plays important roles in hemostasis and inflammation. Defects in von Willebrand Factor are associated with von Willebrand’s disease, one of the most common bleeding disorders. Inside cells, VWF is stored at high density in rod-shaped organelles called Weibel-Palade bodies. In acute response to vascular damage, endothelial cells release long strings of VWF that bind platelets to form a plug. Structural studies of Weibel-Palade bodies therefore shed light on how storage organelles are formed and how their contents are released in response to signals during normal cell function and in disease.
Peter Rosenthal (pictured), in NIMR’s Division of Physical Biochemistry, has collaborated with Tom Carter and Matthew Hannah in the Division of Molecular Neuroendocrinology to obtain 3D images of von Willebrand Factor. In their study, endothelial cells are grown on flat carbon supports and “vitrified” or rapidly cooled before ice can form, which would damage cellular structure. The cells are imaged below -190 °C in the electron microscope using low dose procedures to minimize damage caused by the electron beam. In tomography, images of a cell are recorded from many different orientations to calculate three-dimensional reconstructions of the cell interior. Tomograms show that Weibel-Palade bodies contain helices of VWF tightly associated in a paracrystal.
Cell periphery with Weibel Palade bodies
Tomogram section shows cell periphery with Weibel Palade bodies, microtubule and multivesicular bodies.
This work has given us some of the most exciting pictures ever recorded of the inside of a cell. The structural interaction of proteins and membranes in complex assemblies has been preserved in greater detail than before. We used computational image analysis to extract the very weak signal in low electron dose images and build three-dimensional models of cell architecture. The periphery of the endothelial cell is extremely thin, making images recorded there easier to interpret, and making these cells an excellent system for studying the structural biology of the cell.
Peter Rosenthal
Original article
The research findings are published in full in:
John A. Berriman, Sam Lib, Lindsay J. Hewlett, Sebastian Wasilewski, Fedir N. Kiskin, Tom Carter, Matthew J. Hannah, and Peter B. Rosenthal (2009) Structural organization of Weibel-Palade bodies revealed by cryo-EM of vitrified endothelial cells Proceedings of the National Academy of Sciences, USA, epub ahead of print. Publisher abstract
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