title: High-Curvature Nanostructuring Enhances Probe Display for Biomolecular Detection.
abstract: High-curvature electrodes facilitate rapid and sensitive detection of a broad class of molecular analytes. These sensors have reached detection limits not attained using bulk macroscale materials. It has been proposed that immobilized DNA probes are displayed at a high deflection angle on the sensor surface, which allows greater accessibility and more efficient hybridization. Here we report the first use of all-atom molecular dynamics simulations coupled with electrochemical experiments to explore the dynamics of single-stranded DNA immobilized on high-curvature versus flat surfaces. We find that high-curvature structures suppress DNA probe aggregation among adjacent probes. This results in conformations that are more freely accessed by target molecules. The effect observed is amplified in the presence of highly charged cations commonly used in electrochemical biosensing. The results of the simulations agree with experiments that measure the degree of hybridization in the presence of mono-, di-, and trivalent cations. On high-curvature structures, hybridization current density increases as positive charge increases, whereas on flat electrodes, the trivalent cations cause aggregation due to electrostatic overscreening, which leads to decreased current density and less sensitive detection.
authors.affiliation: Computational Biology Center, IBM Thomas J. Watson Research Center , Yorktown Heights, New York 10598, United States.
authors.forename: Phil
authors.initials: P
authors.lastname: De Luna
authors.forename: Sahar S
authors.initials: SS
authors.lastname: Mahshid
authors.forename: Jagotamoy
authors.initials: J
authors.lastname: Das
authors.affiliation: Computational Biology Center, IBM Thomas J. Watson Research Center , Yorktown Heights, New York 10598, United States.
authors.forename: Binquan
authors.initials: B
authors.lastname: Luan
authors.forename: Edward H
authors.initials: EH
authors.lastname: Sargent
authors.forename: Shana O
authors.identifier: 0000-0003-3360-5359
authors.initials: SO
authors.lastname: Kelley
authors.affiliation: Computational Biology Center, IBM Thomas J. Watson Research Center , Yorktown Heights, New York 10598, United States.|Institute of Quantitative Biology and Medicine, SRMP and RAD-X, Collaborative Innovation Center of Radiological Medicine of Jiangsu Higher Education Institutions, Soochow University , Suzhou 215123, China.|Department of Chemistry, Columbia University , New York, New York 10027, United States.
authors.forename: Ruhong
authors.identifier: 0000-0001-8624-5591
authors.initials: R
authors.lastname: Zhou
mesh_terms: D015374:Biosensing Techniques / Q000379:methods*; D002412:Cations / Q000737:chemistry; D015342:DNA Probes / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry*; D055664:Electrochemical Techniques; D006046:Gold / Q000737:chemistry; D006801:Humans; D061925:Immobilized Nucleic Acids / Q000737:chemistry; D008839:Microelectrodes; D056004:Molecular Dynamics Simulation; D049329:Nanostructures / Q000737:chemistry*; D009693:Nucleic Acid Hybridization; D010316:Particle Size; D013499:Surface Properties
chemical_list: D002412:Cations; D015342:DNA Probes; D004277:DNA, Single-Stranded; D061925:Immobilized Nucleic Acids; D006046:Gold
keywords: DNA hybridization; Molecular dynamics; biosensing; high-curvature effects; nanostructured microelectrodes