Quantum Dots Interaction with α-Actinin via Experimental Observations and Computational Predictions.

Quantum Dots (QDs) are nanoparticles that are highly desirable for biomedical applications such as drug delivery, cellular tracking, and imaging due to their fluorescent and tunable optical properties. However, the biochemical mechanism of their interaction with intracellular proteins that regulate cytoskeletal organization remains poorly understood. While previous studies have shown QDs' ability to interact with actin and alter actin dynamics, their impacts on actin-binding proteins have not been explored. In this study, we investigated the interaction between CdSe/ZnS QDs and the actin-binding protein, α-actinin, and assessed its impact on actin cytoskeletal organization. Our results demonstrated a strong interaction between QDs and α-actinin, which impeded an α-actinin-mediated filamentous actin (F-actin) bundling, as well as compromised the activity of α-actinin in preventing actin depolymerization. Furthermore, the physics-based modeling and simulations carried out at physiological temperatures supported these findings by identifying stable interaction surfaces between QDs and α-actinin. This study provides mechanistic insight into nanoparticle-protein interactions and highlights the potential cytoskeletal toxicity associated with it.