Deciphering Structural Dynamics of DNA-Surfactant Interactions Using the Isomorphic Nucleobase Analogue

The interaction between DNA and surfactants plays an important role in exploring gene regulation, drug delivery, and nanotechnology. However, the specific interactions with the cationic surfactant leading to the conformational changes in DNA are mainly unknown. This study examines the structure and dynamics of DNA-CTAB interactions using the photophysical properties of 2-aminopurine (2Ap)-labeled single-stranded (2Ap-ssDNA) and double-stranded (2Ap-dsDNA) DNA. CTAB induces cooperative compaction in 2Ap-ssDNA, characterized by fluorescence quenching, spectral red shift, and the formation of aligned lamellar aggregates observed in SEM images and XRD analysis. In contrast, dsDNA undergoes compaction/condensation, manifested by fluorescence enhancement, increased fluorescence lifetime, and mixed lamellar and hexagonal aggregates in SEM and XRD data, suggesting structural denaturation/collapse and compaction/condensation. Circular dichroism (CD) analysis corroborates these findings, showing complete disruption of the B-form structure in 2Ap-dsDNA and enhanced strand compaction in 2Ap-ssDNA. Computational studies, including molecular docking, molecular dynamics simulations, and MM/PBSA calculations, support the experimental observations, revealing that CTAB monomer and micelles bind to dsDNA and ssDNA, driven by electrostatic and hydrophobic interactions. These findings underscore the distinct structural responses of 2Ap-ssDNA and 2Ap-dsDNA to surfactant binding. Overall, this study provides valuable insights into the molecular mechanisms of DNA-surfactant interactions and offers a framework for designing DNA-based nanostructures and therapeutic carriers, leveraging electrostatic and hydrophobic forces to modulate nucleic acid architecture for targeted applications.