HIGH-RESOLUTION CRYOSCANNING ELECTRON-MICROSCOPY STUDY OF THE MACROMOLECULAR STRUCTURE OF FIBRONECTIN FIBRILS

High-resolution cryo-scanning electron microscopy was used to examine fibronectin fibrils formed in culture by human skin fibroblasts and in a cell-free system by denaturing soluble plasma fibronectin with guan idine. These studies indicate that the conformation of fibrils formed in culture and in a cell-free system appeared to be similar and that f ibronectin fibrils have at least two distinct structural conformations . Fibronectin fibrils can be very straight structures with smooth surf aces or highly nodular structures. The average diameter of the nodules in these fibrils is 12 nm. Both conformations can be seen within an i ndividual fibril indicating that they are not different types of fibro nectin fibrils but rather different conformational states. Immunolabel ing studies with a monoclonal antibody, IST-2, to the heparin IT bindi ng domain of fibronectin revealed that the epitope was buried in highl y smooth fibrils, but it was readily exposed in nodular fibrils. We pr opose, therefore, that fibronectin fibrils are highly flexible structu res and, depending on the conformation of the fibril, certain epitopes on the surface may be buried or exposed.