Binding between DNA and Carbon Nanotubes Strongly Depends upon Sequence and Chirality

Certain single-stranded DNA (ssDNA) sequences are known to recognize their partner single-walled carbon nanotube (CNT). Here, we report on activation energies for the removal of several ssDNA sequences from a few CNT species by a surfactant molecule. We find that DNA sequences systematically have higher activation energy on their CNT recognition partner than on non-partner species. For example, the DNA sequence (TAT)₄ has much lower activation energy on the (9,1) CNT than on its partner (6,5) CNT, whereas the DNA sequence (CCA)₁₀ binds strongly to its partner (9,1) CNT compared to (6,5) CNT. The (6,5) and (9,1) CNTs have the same diameter but different electronic properties, suggesting that the activation energy difference is related to electronic properties. The activation energies of increasing lengths of closely related sequences from the 11-mer (TAT)₃TA to the 21-mer (TAT)₇ on three different CNT species (9,1), (6,5), and (8,3) were measured. For the shorter sequences, the activation energy on the CNT varies periodically with the sequence

Energetic Basis of Single-Wall Carbon Nanotube Enantiomer Recognition by Single-Stranded DNA

Hybrids of single-stranded DNA and single-walled carbon nanotubes (SWCNTs) have proven to be very successful in separating various chiralities and, recently, enantiomers of carbon nanotubes using aqueous two-phase separation. This technique sorts objects based on small differences in hydration energy, which is related to corresponding small differences in structure. Separation by handedness requires that a given ssDNA sequence adopt different structures on the two SWCNT enantiomers. Here we study the physical basis of such selectivity using a coarse-grained model to compute the energetics of ssDNA wrapped around an SWCNT. Our model suggests that difference by handedness of the SWCNT requires spontaneous twist of the ssDNA backbone. We also show that differences depend sensitively on the choice of DNA sequence

Structural Characteristics of Oligomeric DNA Strands Adsorbed onto Single-Walled Carbon Nanotubes

The single-stranded DNA to single-walled carbon nanotube (SWCNT) hybrid continues to attract significant interest as an exemplary biological molecule–nanomaterial conjugate. In addition to their many biomedical uses, such as in vivo sensing and delivery of molecular cargo, DNA-SWCNT hybrids enable the sorting of SWCNTs according to their chirality. Current experimental methods have fallen short of identifying the actual structural ensemble of DNA adsorbed onto SWCNTs that enables and controls several of these phenomena. Molecular dynamics (MD) simulation has been a useful tool for studying the structure of these hybrid molecules. In recent studies, using replica exchange MD (REMD) simulation we have shown that novel secondary structures emerge and that these structures are DNA-sequence and SWCNT-type dependent. Here, we use REMD to investigate in detail the structural characteristics of two DNA-SWCNT recognition pairs: (TAT)₄-(6,5)-SWCNT, i.e., DNA sequence TAT­TAT­TAT­TAT bound to the (6,5) chirality SWCNT, and (CCG)₂CC-(8,7)-SWCNT as well as off-recognition pairs (TAT)₄-(8,7)-SWCNT and (CCG)₂CC-(6,5)-SWCNT. From a structural clustering analysis, dominant equilibrium structures are identified and show a right-handed self-stitched motif for (TAT)₄-(6,5) in contrast to a left-handed β-barrel for (CCG)₂CC-(8,7). Additionally, characteristics such as DNA end-to-end distance, solvent accessible SWCNT surface area, DNA hydrogen bonding between bases, and DNA dihedral distributions have been probed in detail as a function of the number of DNA strands adsorbed onto the nanotube. We find that the DNA structures adsorbed onto a nanotube are also stabilized by significant numbers of non-Watson–Crick hydrogen bonds (intrastrand and interstrand) in addition to π–π stacking between DNA bases and nanotube surface and Watson–Crick pairs. Finally, we provide a summary of DNA structures observed for various DNA-SWCNT hybrids as a preliminary set of motifs that may be involved in the functional role of these hybrids

Penetration of Cell Surface Glycocalyx by Enveloped Viruses Is Aided by Weak Multivalent Adhesive Interaction

Viral infection usually begins with adhesion between the viral particle and viral receptors displayed on the cell membrane. The exterior surface of the cell membrane is typically coated with a brush-like layer of molecules, the glycocalyx, that the viruses need to penetrate. Although there is extensive literature on the biomechanics of virus–cell adhesion, much of it is based on continuum-level models that do not address the question of how virus/cell-membrane adhesion occurs through the glycocalyx. In this work, we present a simulation study of the penetration mechanism. Using a coarse-grained molecular model, we study the force-driven and diffusive penetration of a brush-like glycocalyx by viral particles. For force-driven penetration, we find that viral particles smaller than the spacing of molecules in the brush reach the membrane surface readily. For a given maximum force, viral particles larger than the minimum spacing of brush molecules arrest at some distance from the membrane, governed by the balance of elastic and applied forces. For the diffusive case, we find that weak but multivalent attraction between the glycocalyx molecules and the virus effectively leads to its engulfment by the glycocalyx. Our finding provides potential guidance for developing glycocalyx-targeting drugs and therapies by understanding how virus–cell adhesion works

Brownian Dynamics Simulation of Peeling a Strongly-Adsorbed Polymer Molecule from a Frictionless Substrate

We used Brownian dynamics to study the peeling of a polymer molecule, represented by a freely jointed chain, from a frictionless surface in an implicit solvent with parameters representative of single-stranded DNA adsorbed on graphite. For slow peeling rates, simulations match the predictions of an equilibrium statistical thermodynamic model. We show that deviations from equilibrium peeling forces are dominated by a combination of Stokes (viscous) drag forces acting on the desorbed section of the chain and a finite rate of hopping over a desorption barrier. Characteristic velocities separating equilibrium and nonequilibrium regimes are many orders of magnitude higher than values accessible in force spectroscopy experiments. Finite probe stiffness resulted in disappearance of force spikes due to desorption of individual links predicted by the statistical thermodynamic model under displacement control. Probe fluctuations also masked sharp transitions in peeling force between blocks of distinct sequences, indicating limitation in the ability of single-molecule force spectroscopy to distinguish small differences in homologous molecular structures

Derivation of Displacement and Stress Fields from Effect of surface bending and stress on the transmission of line force to an elastic substrate

Derivation of displacement and stress Fields by a stream functio

Quantifying Interactions between DNA Oligomers and Graphite Surface Using Single Molecule Force Spectroscopy

In single molecule force spectroscopy experiments, force probes chemically modified with synthetic, single-stranded DNA oligomers produced characteristic steady-state forces connected by abrupt steps between plateaus, as the probes moved away from a graphite substrate. The force plateaus represent peeling of a small number of polymer molecules from the flat surface. The final force jump in the retraction region of the force–distance curves can be attributed to a single DNA molecule detaching from the graphite surface. Previously, Manohar et al. (<i>Nano Lett.</i> <b>2008</b>, <i>8</i>, 4365) reported the peeling forces of the pyrimidine oligomers as 85.3 ± 4.7 and 60.8 ± 5.5 pN for polythymine and polycytosine, respectively. We measured the force–distance curves for purine oligomers on a graphite surface and found the peeling forces to be 76.6 ± 3.0 and 66.4 ± 1.4 pN for polyadenine and polyguanine, respectively. Using a refined model for peeling a single freely jointed polymer chain from a frictionless substrate, we determined a ranking of the effective average binding energy per nucleotide for all four bases as T ≥ A > G ≥ C (11.3 ± 0.8, 9.9 ± 0.5, 8.3 ± 0.2, and 7.5 ± 0.8 <i>k</i>_B<i>T</i>, respectively). The binding energy determined from the peeling force data did not scale with the size of the base. The distribution of peeling forces of polyguanine from the graphite surface was unusually broad in comparison to the other homopolymers, and often with inconsistent chain extensions, possibly indicating the presence of secondary structures (intra- or intermolecular) for this sequence

DNA Conjugated SWCNTs Enter Endothelial Cells via Rac1 Mediated Macropinocytosis

Several applications of single-walled carbon nanotubes (SWCNT) as nanovectors in biological systems have been reported, and several molecular pathways of cellular entry have been proposed. We employed transmission electron microscopy, confocal fluorescent microscopy, and UV–vis spectroscopic analysis to confirm the internalization of DNA-SWCNT in human umbilical vein endothelial cells. Additionally, by using pharmacological inhibitors as well as genetic approaches, we have found that SWCNT is endocytosed through Rac1- GTPase mediated macropinocytosis in normal endothelial cells

Indentation versus Rolling: Dependence of Adhesion on Contact Geometry for Biomimetic Structures

Numerous biomimetic structures made from elastomeric materials have been developed to produce enhancement in properties such as adhesion, static friction, and sliding friction. As a property, one expects adhesion to be represented by an energy per unit area that is usually sensitive to the combination of shear and normal stresses at the crack front but is otherwise dependent only on the two elastic materials that meet at the interface. More specifically, one would expect that adhesion measured by indentation (a popular and convenient technique) could be used to predict adhesion hysteresis in the more practically important rolling geometry. Previously, a structure with a film-terminated fibrillar geometry exhibited dramatic enhancement of adhesion by a crack-trapping mechanism during indentation with a rigid sphere. Roughly isotropic structures such as the fibrillar geometry show a strong correlation between adhesion enhancement in indentation versus adhesion hysteresis in rolling. However, anisotropic structures, such as a film-terminated ridge-channel geometry, surprisingly show a dramatic divergence between adhesion measured by indentation versus rolling. We study this experimentally and theoretically, first comparing the adhesion of the anisotropic ridge-channel structure to the roughly isotropic fibrillar structure during indentation with a rigid sphere, where only the isotropic structure shows adhesion enhancement. Second, we examine in more detail the anomalous anisotropic film-terminated ridge-channel structure during indentation with a rigid sphere versus rolling to show why these structures show a dramatic adhesion enhancement for the rolling case and no adhesion enhancement for indentation

Quantification of DNA/SWCNT Solvation Differences by Aqueous Two-Phase Separation

Single-walled carbon nanotubes (SWCNTs) coated with single-stranded DNA can be effectively separated into various chiralities using an aqueous two-phase (ATP) system. Partitioning is driven by small differences in the dissolution characteristics of the hybrid between the two phases. Thus, in addition to being a separation technique, the ATP system potentially also offers a way to quantify and rank the dissolution properties of the solute (here the DNA/SWCNT hybrids), such as the solvation free energy and solubility. In this study, we propose two different approaches to quantitatively analyze the ATP partitioning of DNA/SWCNT hybrids. First, we present a model that extracts the relative solvation free energy of various DNA/SWCNT hybrids by using an expansion relative to a standard state. Second, we extract a solubility parameter by analyzing the partitioning of hybrids in the ATP system. The two approaches are found to be consistent, providing some confidence in each as a method of quantifying differences in the solubility of various DNA/SWCNT hybrids