Three Dimensional Molecular Scale Imaging of Plasma Proteins Under Aqueous Conditions

Abstract

Atomic force microscopy (AFM) provides unique opportunities to study cell-surface and molecular scale interactions in three dimensions under aqueous conditions. In AFM, a small probe attached to cantilever (fig. 1) is used for interacting with a sample to obtain sensitive measurements of molecular structure, intermolecular forces (sub-nN) and interfacial properties. The data ouput can be presented in the form of a topographical image, force map or viscoelastic response (e.g., Figs. 2-4). Thus, AFM combines high resolution imaging with the ability to measure surface-dependent intermolecular forces and properties. AFM also is amenable for coupling with optical imaging methods including immunofluoresence and gold bead labeling.This presentation will focus primarily on the use of AFM for molecular level imaging of plasma proteins, von Willebrand Factor (vWF) and fibrinogen. Both proteins play central roles in the regulation of hemostasis and thrombosis by participating in coagulation or by facilitating adhesion, spreading and aggregation of activated platelets.