Electron Microscopic Studies of the Factor VIII-Von Willebrand Factor Protein

Preparations of human Factor VIII which were homogemeous by SDS-polyacrylamide gel electrophoresis were examined by electron microscopy after negative staining with phosphotungstic acid. Most striking were large oval and circular forms, usually present in loose groupings of four or more molecules. Approximately 80% were oval-shaped and the mean axial dimensions of 167 such molecules, considered to be prolate ellipsoids, were 725 Å and 346 Å (axial ratio about 2rl). The 34 circular forms had a mean diameter of 545 Å and were considered to represent a separate though related molecular entity, either of spherical or oblate ellipsoidal shape. A variety of smaller forms was also present in these preparations including round molecules of 110–330 Å in diameter, irregular ovoid shapes with filamentous transformation and filaments of variable length and thickness. Based on calculations of volume relative to that of fibrinogen, the molecular weight of the predominant prolate ellipsoid form is about 3 million daltons, a value which is consistent with reported estimates of molecular size obtained by ultracentrifuge or gel filtration studies.