Electrochemical DNA biosensors utilizing self-assembled monolayers (SAMs) with inserted DNA probes are a promising biosensor design due to their ease of preparation, miniaturization, and tunability. However, much is still unknown about the dynamics and intermolecular interactions of biomolecules like DNA on various sensor surfaces. A fundamental question regarding these sensors concerns the nature of surface diffusion of target molecules and whether it speeds up the molecular recognition process. Lack of understanding of molecular interaction and diffusion in addition to questions regarding the behavior of DNA probes immobilized on the sensor surface currently limit the rational design of such biosensors. Using all-atom unbiased molecular dynamics (MD) simulations we found that 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 they are considerably more stable in certain SAMs than others, which affects the ability of probes to remain elongated and upright and is likely to change DNA hybridization kinetics in multiple ways. We also found that nearby probes can alter each other’s orientations dramatically, highlighting the importance of surface density control as the accessibility of probes to target molecules has profound influence on molecular recognition. Our results elucidate nucleic acid biosensor dynamics vital to rational design and offer insight that can aid in the development of application-specific surface chemistry and patterning.

Dynamics and molecular interactions of ssDNA in nucleic acid biosensors with varied surface properties

2019 Fall National Meeting

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