(194h) Molecular Interaction of DNA with Cysteamine- and Polylysine-Acetate Modified Gold Surfaces for Single Nucleobase Identification
Three different surface modifications on Au(111) surfaces were tested: (1) long-chain polylysine acetate (degree of polymerization = 30), (2) fully protonated cysteamine acetate, and (3) mixed cysteamine/protonated cysteamine acetate. All systems are overall electroneutral. The polylysine monolayers are most stably bound to the surface, as tested in the simulation by annealing, and a few acetate molecules migrate to the Au surface. The cysteamine monolayers experience minor desorption and surface replacement by acetate or water molecules. All modified gold (111) surfaces strongly bind the negatively charged DNA via electrostatic interactions and prohibit coiling upon adsorption. Some backbone contortion occurs depending on the type of monolayer. The fully ionized cysteamine monolayer is abundant with positively charged ammonium groups available for binding to the phosphate backbone, resulting in minor bending of the DNA backbone and adsorption in a relatively linear confirmation. This arrangement would allow for the highest number of nucleobases to be identified as fewer bases adsorb flat-on on this monolayer (tilting is preferred for a clear readout in experiment). As the monolayer is entirely ionized, an acetate counterion is present for each cysteamine ligand, and blocks a majority of the nucleobases from adsorbing flat-on to the surface. However, some bases may not be identifiable as some acetate ions migrate to the Au surface and leave a number of cysteamines unoccupied, resulting in adsorption of both backbone and nucleobase. The polylysine monolayer is similar to the fully protonated cysteamine acetate surface, however, since it consist of many long chains of lysine, the DNA attempts to bind parallel to the chain configuration of polylysines on the surface, resulting in contortions of the phosphate backbone. This surface might allow the identification of fewer bases the fully ionized cysteamine surface. Finally, the mixed neutral cysteamine/protonated cysteamine acetate surface has fewer sites for backbone adsorption. This results in bending of the DNA backbone in order to adsorb on the protonated cysteamine residues and avoiding the neutral ligands. The likely result are much fewer identifiable nucleobases. The availability of many neutral surface ligands allows the nucleobases to interact with the monolayer through weak interactions, resulting in complete binding of some of the bases, and no tilt as required for laser reading.
Afsari, S., Korshoj, L. E., Abel, G. R., Jr., Khan, S., Chatterjee, A., & Nagpal, P. (2017). Quantum Point Contact Single-Nucleotide Conductance for DNA and RNA Sequence Identification. ACS Nano, 11(11), 11169-11181. doi: 10.1021/acsnano.7b05500
Korshoj, L. E., Afsari, S., Chatterjee, A., & Nagpal, P. (2017). Conformational Smear Characterization and Binning of Single-Molecule Conductance Measurements for Enhanced Molecular Recognition. J Am Chem Soc, 139(43), 15420-15428. doi: 10.1021/jacs.7b08246
Korshoj, L. E., Afsari, S., Khan, S., Chatterjee, A., & Nagpal, P. (2017). Single Nucleobase Identification Using Biophysical Signatures from Nanoelectronic Quantum Tunneling. Small, 13(11). doi: 10.1002/smll.201603033