This work has focused on the structural basis and molecular mechanisms of blood clotting. Much of the work has been concerned with the structure and assembly of the fibrin clot. Using the techniques of conventional transmission and scanning electron microscopy, this laboratory previously determined aspects of the intermolecular interactions that constitute clot assembly as well as factors in the plasma and proteins released by platelets that modulate clot structure. With this background, we now are studying in more detail the three-dimensional clot structure using thick preparations and IVEM, also employing the quantitative 3D image processing capability developed in this Resource. Initially, we have quantified the nature and extent of branching of fibers in a clot. Clots formed under a variety of conditions have been found to have very different structures: the extent of lateral aggregation and thickness of the fiber bundles and the sizes of the pores vary greatly. We are now refining these studies to determine distances between branch points and angles between branching fibers from stereo pairs using the programs developed in this Resource. We also are extending our 3D network reconstruction programs to deal with images showing superimposed filamentous structures that do not form a network, i.e. do not intersect. Both manual and automated reconstruction programs are using images from this project as test objects in that technological development.
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