Atomic force microscopy (AFM) provides unique opportunities to study cell-surface and molecular scale interactions in three dimensions under aqueous conditions. Two plasma proteins, von Willebrand Factor (vWf) and fibrinogen, play central roles in the regulation of hemostasis and thrombosis by participating in coagulation and facilitating adhesion and aggregation of activated platelets. vWf and fibrinogen are believed to facilitate platelet adhesion under regions of relatively high and low vascular wall shear stress, respectively. Consequently, elucidating vWf and fibrinogen structure-function relations under shear is of considerable importance in developing a comprehensive understanding of the pathophysiology of thrombogenesis. Previously, we reported on molecular level AFM images of human vWf during shear-induced structural transition and human fibrinogen under aqueous conditions when both proteins were adsorbed on a hydrophobic surface. This presentation will report on the shear dependent interactions of dimeric and multimeric vWf with a hydrophobic surface and the substrate-dependent interactions of fibrinogen.