Chirality of gold nanocluster affects its interaction with coagulation factor XII

Probing the interaction of nanomaterials (NMs) with proteins is the basic step for biological safety assessment. Many physiochemical factors of NMs play important roles in binding with proteins as they determine the binding process. Among them, the chirality-related biological effects and nanotoxicology have not been fully understood. As NMs are mainly exposed to human circulatory system with intentional or unintentional exposure, understanding the interaction mechanism of plasma functional proteins with chiral NMs is of great importance. Herein, we show the interaction of chiral gold nanoclusters (AuNCs), L- and D-cysteine coated AuNC (i.e., L-AuNC and D-AuNC, respectively) with human coagulation factor XII (FXII, an important plasma zymogen initiating the inner coagulation system). D-AuNC exhibited weak binding affinity for FXII, induced FXII aggregation due to significant conformational change, which then activated the FXII for further cleavage. In contrast to D-AuNC, the binding affinity of L-AuNC for FXII was strong and their bioconjugate was quite stable without aggregation. L-AuNC induced the structural change and autoactivation of FXII to a lower extent. Moreover, the enzymatic activity of FXIIa (the activated form of FXII) was influenced upon incubation with L- AuNCs and D-AuNCs with different molecular mechanisms. The finding will expand the understanding of the nanobiological effects of chiral NMs and suggest the potential application in nanomedicine.