Non-covalent interactions between single-stranded DNA (ssDNA) oligonucleotides and single wall carbon nanotubes (SWNTs) have provided a unique class of tunable chemistries for a variety of applications. However, mechanistic insight into both the photophysical and intermolecular phenomena underlying their utility is lacking, resulting in obligate heuristic approaches for producing ssDNA-SWNT based technologies. In this work, we present an ultrasensitive “turn-on” nanosensor for neuromodulators dopamine and norepinephrine with strong relative change in fluorescence intensity (ΔF/F0) of up to 3500%, a signal appropriate for in vivo neuroimaging, and uncover the photophysical principles and intermolecular interactions that govern the molecular recognition and fluorescence modulation of this nanosensor synthesized from the spontaneous self-assembly of (GT)6 ssDNA rings on SWNTs. The fluorescence modulation of the ssDNA-SWNT conjugate is shown to exhibit remarkable sensitivity to the ssDNA sequence chemistry, length, and surface density, providing a set of parameters with which to tune nanosensor dynamic range and strength of fluorescence turn-on. We employ classical and quantum mechanical molecular dynamics simulations to rationalize our experimental findings. Calculations show that (GT)6 ssDNA form ordered rings around SWNT, inducing periodic surface potentials that modulate exciton recombination lifetimes. Further evidence is presented to elucidate how dopamine analyte binding modulates SWNT fluorescence. We discuss the implications of our findings for SWNT-based molecular imaging applications.
There is a noted lack of understood, controllable interactions for directing the organization of collagen triple helices. While the field has had success using charge–pair interactions and cation−π interactions in helix design, these alone are not adequate for achieving the degree of specificity desirable for these supramolecular structures. Furthermore, because of the reliance on electrostatic interactions, designed heterotrimeric systems have been heavily charged, a property undesirable in some applications. Amide−π interactions are a comparatively understudied class of charge-free interactions, which could potentially be harnessed for triple-helix design. Herein, we propose, validate, and utilize pairwise amino acid amide−π interactions in collagen triple-helix design. Glutamine–phenylalanine pairs, when arranged in an axial geometry, are found to exhibit a moderately stabilizing effect, while in the lateral geometry, this pair is destabilizing. Together this allows glutamine–phenylalanine pairs to effectively set the register of triple helices. In contrast, interactions between asparagine and phenylalanine appear to have little effect on triple-helical stability. After deconvoluting the contributions of these amino acids to triple-helix stability, we demonstrate these new glutamine–phenylalanine interactions in the successful design of a heterotrimeric triple helix. The results of all of these analyses are used to update our collagen triple-helix thermal stability prediction algorithm, Scoring function for Collagen Emulating Peptides’ Temperature of Transition (SCEPTTr).
DNA-wrapped single walled carbon nanotubes (SWNTs) have found a widespread use in a variety of nanotechnology applications. Yet, the relationship between structural conformation, binding affinity and kinetic stability of these polymers on SWNTs remains poorly understood. Here, we used molecular dynamics (MD) simulations and experiments to explore this relationship for short oligonucleotides adsorbed on SWNTs. First, using classical MD simulations of oligonucleotide-(9,4)-SWNT hybrid complexes, we explored the relationship between ssDNA and ssRNA surface conformation and sequence chemistry. We screened the conformation of 36 sequences of short ssDNA and ssRNA polymers on (9,4) SWNT, where the contour lengths were selected so the polymers can, to a first approximation, wrap once around the SWNT circumference. From these screens, we identified structural motifs that we broadly classified into "rings" and "non-rings." Then, several sequences were selected for detailed investigations. We used temperature replica exchange MD calculations to compute two-dimensional free energy landscapes characterizing the conformations of select sequences. "Ring" conformations seemed to be driven primarily by sequence chemistry. Specifically, strong (n,n+2) nucleotide interactions and the ability of the polymer to form compact structures, as for example, through sharp bends in the nucleotide backbone, correlated with ring-forming propensity. However, ring-formation probability was found to be uncorrelated with free energy of oligonucleotide binding to SWNTs (∆Gbind). Conformational analyses of oligonucleotides, computed free energy of binding of oligonucleotides to SWNTs, and experimentally determined kinetic stability measurements show that ∆Gbind is the primary correlate for kinetic stability. The probability of the sequence to adopt a compact, ring-like conformation is shown to play a secondary role that still contributes measurably to kinetic stability. For example, sequences that form stable compact rings (C-rich sequences) could compensate for their relatively lower ∆Gbind and exhibit kinetic stability, while sequences with strong ∆Gbind (such as (TG)3(GT)3) were found to be kinetically stable despite their low ring formation propensity. We conclude that the stability of adsorbed oligonucleotides is primarily driven by its free energy of binding and that if ring-like structural motifs form, they would contribute positively to stability.
Many properties and applications of single-wall carbon nanotubes (SWCNTs) depend strongly on the coatings that allow their suspension in aqueous media. We report that SWCNT fluorescence is quenched by reversible physisorption of dye molecules such as methylene blue, and that measurements of that quenching can be used to infer structure-specific exposures of the nanotube surface to the surrounding solution. SWCNTs suspended in single-stranded DNA oligomers show quenching dependent on the combination of nanotube structure and ssDNA base sequence. Several sequences are found to give notably high or low surface coverages for specific SWCNT species. These effects seem correlated with the selective recognitions used for DNA-based structural sorting of nanotubes. One notable example is that dye quenching of fluorescence from SWCNTs coated with the (ATT)4 base sequence is far stronger for one (7,5) enantiomer than for the other, showing that coating coverage is associated with the coating affinity difference reported previously for this system. Equilibrium modeling of quenching data has been used to extract parameters for comparative complexation constants and accessible surface areas. Further insights are obtained from molecular dynamics simulations, which give estimated contact areas between ssDNA and SWCNTs that correlate with experimentally inferred surface exposures and account for the enantiomeric discrimination of (ATT)4.
Understanding the conformations of physisorbed single-stranded DNA (ssDNA) oligos on single-wall carbon nanotube (SWCNT) surfaces is important for advancing basic nanoscience and for developing applications in biomedicine and quantum information processing. Here we report evidence that the ssDNA strands are partly desorbed from the nanotube surface under common conditions. SWCNT suspensions were prepared in eight ssDNA oligos, each containing 1 guanine and 30 thymine bases but differing in the position of the guanine within the strand. Singlet oxygen exposure then covalently functionalized the guanine to the SWCNT surface, red-shifting the nanotube fluorescence by an amount reflecting the guanine spatial density at the surface. Spectral shifts were greatest for central guanine positions and smallest for end positions. In conjunction with steered molecular dynamics simulations, the results suggest that steric interference between neighboring ssDNA strands on an individual nanotube causes significant dislocation or desorption of the strand ends while central regions remain better wrapped around the nanotube. This effect decreases with decreasing concentrations of free ssDNA.
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