Von Willebrand factor (VWF) is secreted as ultralarge multimers that are cleaved in the A2 domain by the metalloprotease ADAMTS13 to give smaller multimers. Cleaved VWF is activated by hydrodynamic forces found in arteriolar bleeding to promote hemostasis, whereas uncleaved VWF is activated at lower, physiologic shear stresses and causes thrombosis. Single-molecule experiments demonstrate that elongational forces in the range experienced by VWF in the vasculature unfold the A2 domain, and only the unfolded A2 domain is cleaved by ADAMTS13. In shear flow, tensile force on a VWF multimer increases with the square of multimer length and is highest at the middle, providing an efficient mechanism for homeostatic regulation of VWF size distribution by force-induced A2 unfolding and cleavage by ADAMTS13, as well as providing a counterbalance for VWF-mediated platelet aggregation.

We present a simple and secure system for encrypting and decrypting information using DNA self-assembly. Binary data is encoded in the geometry of DNA nanostructures with two distinct conformations. Removing or leaving out a single component reduces these structures to an encrypted solution of ssDNA, whereas adding back this missing “decryption key” causes the spontaneous formation of the message through self-assembly, enabling rapid read out via gel electrophoresis. Applications include authentication, secure messaging, and barcoding.

von Willebrand Factor (vWF) is a plasma protein essential to the early stages of blood coagulation. Shear induced proteolysis at the A2 domain of vWF is an important mechanism to convert the highly thrombogenic, ultra large vWF multimers to smaller multimeric forms and, consequently, to prevent overgrown thrombus. It has been hypothesized that the A2 domain undergoes conformational changes in response to tensile force and exposes its Tyr842-Met843 scissile bond for cleavage by ADAMTS13, a metalloprotease found in the circulating blood. In this work, the unfolding and folding kinetics of the A2 domain is studied using optical tweezers under pulling forces that mimicked the tensile forces exposed to vWF multimers in the vasculature. We demonstrate that A2 domain is unstable upon pulling and unfolds at between 7 to 14 pN at loading rates ranging from 0.3 to 300 pN/s. Once unfolded, stressfree refolding of A2 domain takes 1.9 seconds, increasing dramatically with tensile force. Unfolded A2 domain was cleaved by physiological concentration of ADAMTS13 with a catalytic rate constant of 0.14/s. The results suggest that the A2 domain is unraveled at physiological tensile forces in vivo and its slow refolding process ensures the enzymatic reaction of ADAMTS13. Hence, the A2 domain acts as a force sensor that triggers ADAMTS13 cleavage at the pico-newton force range.