SummaryFibrinogen plays a central role in surface-induced thrombosis. However, the interactions of fibrinogen with different substrata remain poorly understood because of the difficulties involved in imaging globular proteins under aqueous conditions. We present detailed three dimensional molecular scale images of fibrinogen molecules on a hydrophobic surface under aqueous conditions obtained by atomic force microscopy. Hydrated fibrinogen monomers are visualized as overlapping ellipsoids; dimers and trimers have linear conformations predominantly, and increased affinity for the hydrophobic surface compared with monomeric fibrinogen. The results demonstrate the importance of hydration on protein structure and properties that affect surface-dependent interactions.

A force transducer with variable sensitivity and speed is described. Its moving element is a cantilever beam that projects vertically into a muscle bath. A brace constrains bending of the beam to a short, proximal "hinge." Rotation of the beam about the hinge is amplified 30-fold by an optical lever consisting of a laser diode beam reflected from a mirror on the cantilever to a photodiode pair. This design places the electrical components at a distance from the damp environment of the muscle bath. Large changes in sensitivity and speed can be obtained by substituting different cantilevers. Smaller changes can be made by varying the length of the hinge. A transducer with a 6-mm cantilever optimized for the study of single, skinned skeletal muscle fibers is described in detail. This device had a resonant frequency of 22 kHz and sensitivity such that the total root-mean-square noise in the circuit was more than 500-fold smaller than the expected maximum force. Variations of this device with orders of magnitude different sensitivities are also described.