Dynamics and molecular interactions of single-stranded DNA in nucleic acid biosensors with varied surface properties

Electrochemical DNA biosensors utilizing self-assembled monolayers (SAMs) with inserted DNA probes are promising biosensor designs because of their ease of preparation, miniaturization, and tunability. However, much is still unknown about the interactions between biomolecules such as DNA and various surfaces. A fundamental question regarding these sensors concerns the nature of diffusion of target molecules taking place on sensor surfaces and whether it speeds up the molecular recognition process. Lack of understanding of molecular interaction and surface diffusion in addition to questions regarding the behavior of DNA probes immobilized on these surfaces currently limits the rational design of nucleic acid biosensors. Using all-atom unbiased molecular dynamics (MD) simulations we found that single-stranded DNA (ssDNA) behavior on SAMs is drastically altered by different surface chemistries, with ssDNA adopting very different orientations upon adsorption and surface diffusivity varying over an order of magnitude. Probe behavior varies equally broadly as probes are considerably more stable in certain SAMs than others, which affects the accessibility of probes to the target molecules and likely changes DNA hybridization kinetics in multiple ways. We also found that nearby probes can alter each other's orientations substantially, which highlights the importance of surface density control. Our results elucidate nucleic acid biosensor dynamics vital to rational design and offer insights that can aid in the design of surface properties and patterning for specific applications.