Electric Field-Driven Modulation of Nanomechanical Interactions Between Tyrosine Kinase Inhibitors and Human Serum Albumin: Insights from AFM-Based Force Spectroscopy

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 (<i>F_i</i>) and non-specific (<i>F</i>₀) force, friction behavior, and protein morphology. Increasing field strength led to significant reductions in adhesion force (22-47%), <i>F_i</i> (27-44%), <i>F</i>₀ (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.