The Molecular Structure Of Fibrinogen And The Architecture Of The Fibrin Clot: A Model From Electron Microscopy

The shape of the fibrinogen molecule and aspects of its packing to form fibrin have been derived from a study of electron microscope images of crystals and microcrystals. Using coordinated X-ray diffraction and electron microscopy, the length of the molecule was eastblished as 450Å. The molecules bond end-to-end to form filaments whose packing could be determined for several crystalline forms. A particularly useful aggregate in establishing the shape of the molecule was a “segment“ form of modified human fibrinogen that reveals direct information about the mass distribution. Computer simulations were carried out to refine the size and location of the globular domains. A single molecular model was derived to account for the substructure and packing in a variety of arrays seen in the electron microscope. The molecule can be seen in more detail than the tri-nodular Hall-Slayter model, and is made up of seven globular domains connected by rod-like regions.

The molecular architecture of the fibrin clot has been a puzzle for several decades. A simple, half-staggered arrangement of trinodular molecules can account for the 225 Å repeat, but not the detailed features of the band pattern of the negatively stained fibrin in the electron microscope. We can now simulate the fibrin band pattern using the heptad model and a packing arrangement derived from one of the microcrystalline forms. The molecular arrangement in fibrin is complex: the 450 Å long molecules are half staggered and bonded end-to-end; they are also bent and tilted slightly. Further aspects of the structure and packing will be available from the X-ray crystallographic analysis of the hydrated molecule now in progress.