Fig. 3.

Schematic of shear-induced activation of multimeric VWF and subsequent interactions with exposed collagen, ADAMTS-13 and platelet GpIbα receptor. (a) Under low shear stress VWF adopts a compact conformation with the three A domains buried and inaccessible for binding. (b) In case of injury, shear stress increases due to vascular contraction, leading to mechanical unfolding of A2 and exposure of A1 and A3, revealing cryptic binding sites on VWF that interact with collagen, GPIbα and ADAMTS-13. ADAMTS-13 is conformationally activated upon interaction with VWF and cuts the unfolded A2 domain