Objective To investigate the regulatory mechanism of wild-type (WT) and gain-of-function (GOF) ADAMTS13 interaction with VWF A2. Methods The adhesion frequency, rupture force, and bond lifetime between WT or GOF ADAMTS13 and VWF A2 under different external forces were measured by atomic force microscopy. The kinetic parameters were derived by fitting with the Bell-Evans model. Results The widths of the potential barrier along the direction of force were 0.41 nm and 0.29 nm, and the dissociation rates at zero force were 1.50 s-1 and 3.28 s-1 for the WT ADAMTS13-VWF A2 complex and the GOF ADAMTS13-VWF A2 complex respectively. Furthermore, the lifetime of bond and dissociation rate of the complexes under different applied forces were measured by AFM clamp mode. The data revealed that the interaction between WT or GOF ADAMTS13 and VWF A2 exhibited the characteristics of biphasic force-dependent “catch”-“slip” transition bond. Conclusions The mechanical strength and stability of the WT ADAMTS13-VWF A2 complex are higher than those of the GOF ADAMTS13-VWF A2 complex. Both the binding of these two complexes exhibits the mechanical response characteristics of the “catch-slip” transition bond. Our study contributes to further understand the interaction between ADAMTS13 and VWF, and provides new ideas for the development of antithrombotic drugs.