Electric Field-Driven Modulation of Nanomechanical Interactions Between Tyrosine Kinase Inhibitors and Human Serum...

Electric fields are emerging as powerful tools to actively regulate biomolecular interactions at biointerfaces. In this study, we investigated how varying electric field strengths (0-100 mV/mm) influence the interfacial interaction between human serum albumin (HSA) and six tyrosine kinase inhibitors (TKIs): imatinib, bosutinib, dasatinib, nilotinib, ponatinib, and radotinib. Using atomic force microscopy (AFM), we quantified changes in adhesion force, specific (F_i) and non-specific (F₀) force, friction behavior, and protein morphology. Increasing field strength led to significant reductions in adhesion force (22-47%), F_i (27-44%), F₀ (38-53%), friction force (38-67%) and constant-load friction force (43-54%), along with decreased protein average surface height and roughness, indicating electric field-induced molecular compaction and interface smoothing. Notably, more hydrophobic TKIs showed greater responsiveness. These findings highlight the potential of electric fields to modulate protein-drug interactions in a controllable manner, offering a new strategy for the development of electrically tunable drug delivery systems and smart biomedical interfaces.