Phase transitions in DNA-linked nanoparticle assemblies: a decorated-lattice model

We use decorated-lattice models to explore the phase behavior of two types of DNA-linked colloidal mixtures: systems with identical nanoparticles functionalized with two different DNA strands (mixture Aab) and mixtures involving two types of particles each one functionalized with a different DNA strand (mixture Aa-Ab). The model allows us to derive the properties of the mixtures from the well-known behavior of underlying spin-n Ising models with temperature and activity dependent effective interactions. The predicted evolution of the dissolution profiles for the colloidal assemblies as a function of temperature and number of single DNA strands on a nanoparticle M is in qualitative agreement with that observed in real systems. According to our model, the temperature at which the assemblies dissolve can be expected to increase with increasing M only for concentrations of colloids below a certain threshold. For more concentrated solutions, the dissolution temperature is a decreasing function of M. Linker-mediated interactions between Aa and Ab particles in the Aa-Ab mixture render the phase separation involving disordered aggregates metastable with respect to a phase transition between a solvent-rich and an ordered phase. The stability of the DNA-linked assembly is enhanced by the ordering of the colloidal network and the ordered aggregates dissolve at higher temperatures. Our results may explain the contrasting evolution of the dissolution temperatures with increasing probe size in Aab and Aa-Ab mixtures as observed experimentally.     

What controls the melting properties of DNA-linked gold nanoparticle assemblies?

We report a series of experiments and a theoretical model designed to systematically define and evaluate the relative importance of nanoparticle, oligonucleotide, and environmental variables that contribute to the observed sharp melting transitions associated with DNA-linked nanoparticle structures. These variables include the size of the nanoparticles, the surface density of the oligonucleotides on the nanoparticles, the dielectric constant of the surrounding medium, target concentration, and the position of the nanoparticles with respect to one another within the aggregate. The experimental data may be understood in terms of a thermodynamic model that attributes the sharp melting to a cooperative mechanism that results from two key factors: the presence of multiple DNA linkers between each pair of nanoparticles and a decrease in the melting temperature as DNA strands melt due to a concomitant reduction in local salt concentration. The cooperative melting effect, originating from short-range duplex-to-duplex interactions, is independent of DNA base sequences studied and should be universal for any type of nanostructured probe that is heavily functionalized with oligonucleotides. Understanding the fundamental origins of the melting properties of DNA-linked nanoparticle aggregates (or monolayers) is of paramount importance because these properties directly impact one's ability to formulate high sensitivity and selectivity DNA detection systems and construct materials from these novel nanoparticle materials.     

Defects can increase the melting temperature of DNA-nanoparticle assemblies

DNA-gold nanoparticle assemblies have shown promise as an alternative technology to DNA microarrays for DNA detection and RNA profiling. Understanding the effect of DNA sequences on the melting temperature of the system is central to developing reliable detection technology. We studied the effects of DNA base-pairing defects, such as mismatches and deletions, on the melting temperature of DNA-nanoparticle assemblies. We found that, contrary to the general assumption that defects lower the melting temperature of DNA, some defects increase the melting temperature of DNA-linked nanoparticle assemblies. The effects of mismatches and deletions were found to depend on the specific base pair, the sequence, and the location of the defects. Our results demonstrate that the surface-bound DNA exhibit hybridization behavior different from that of free DNA. Such findings indicate that a detailed understanding of DNA-nanoparticle assembly phase behavior is required for quantitative interpretation of DNA-nanoparticle aggregation.     

Clustering versus percolation in the assembly of colloids coated with long DNA

We report an experimental study in which we compare the self-assembly of 1 mum colloids bridged through hybridization of complementary single-stranded DNA (ssDNA) strands (12 bp) attached to variable-length double-stranded DNA spacers that are grafted to the colloids. We considered three different spacer lengths: long spacers (48 500 bp), intermediate length spacers (7500 bp), and no spacers (in which case the ssDNA strands were directly grafted to the colloids). In all three cases, the same ssDNA pairs were used. However, confocal microscopy revealed that the aggregation behavior is very different. Upon cooling, the colloids coated with short and intermediate length DNAs undergo a phase transition to a dense amorphous phase that undergoes structural arrest shortly after percolation. In contrast, the colloids coated with the longest DNA systematically form finite-sized clusters. We speculate that the difference is due to the fact that very long DNA can easily be stretched by the amount needed to make only intracluster bonds, and in contrast, colloids coated with shorter DNA always contain free binding sites on the outside of a cluster. The grafting density of the DNA decreases strongly with increasing spacer length. This is reflected in a difference in the temperature dependence of the aggregates: for the two systems coated with long DNA, the resulting aggregates were stable against heating, whereas the colloids coated with ssDNA alone would dissociate upon heating.     

Sharp melting in DNA-linked nanostructure systems: thermodynamic models of DNA-linked polymers

Sharp melting that has been found for DNA-linked nanostructure systems such as DNA-linked gold nanoparticles enhances the resolution of DNA sequence detection enough to distinguish between a perfect match and single base pair mismatches. One intriguing explanation of the sharp melting involves the cooperative dehybridization of DNA strands between the nanostructures. However, in the DNA-linked gold nanoparticle system, strong optical absorption by the gold nanoparticles hinders the direct observation of cooperativity. Here, with a combination of theory and experiment, we investigate a DNA-linked polymer system in which we can show that the optical profile of the system at 260 nm is directly related to the individual DNA dehybridization profile, providing a clear distinction from other possible mechanisms. We find that cooperativity plays a crucial role in determining both the value of the melting temperature and the shape of the melting profile well away from the melting temperature. Our analysis suggests that the dehybridization properties of DNA strands in confined or dense structures differ from DNA in solution.     

Nanoparticle-based electrochemical DNA detection

Nanoscale architectures of DNA-linked particle networks are attractive for electrical detection of DNA hybridization. This article reviews a variety of new nanoparticle/polynucleotide assemblies for advanced electrical detection of DNA sequences. Recent activity has led to innovative and powerful nanoparticle-based electrochemical DNA hybridization assays based on a variety of detection schemes. Such protocols rely on the use of colloidal gold tags, semiconductor quantum dot tracers, polymeric carrier (amplification) beads, or magnetic (separation) beads. Particularly useful have been protocols based on capturing of metal nanoparticle tracers followed by dissolution and anodic-stripping voltammetric measurement of the metal tag. Remarkable sensitivity is achieved by coupling particle-based amplification units and various amplification processes. The use of nanoparticle tracers for designing multi-target electrochemical coding protocols will also be documented.     

Molecular dynamics studies of ion distributions for DNA duplexes and DNA clusters: salt effects and connection to DNA melting

We present extensive molecular dynamics simulations of the ion distributions for DNA duplexes and DNA clusters using the Amber force field with implicit water. The distribution of ions and the electrostatic energy of ions around an isolated DNA duplex and clusters of DNA duplexes in different salt (NaCl) concentrations over the range 0.2-1.0 mol/L are determined on the basis of the simulation results. Using the electrostatic energy profile, we determine a local net charge fraction phi, which is found to increase with increasing of salt concentration. For DNA clusters containing two DNA duplexes (DNA pair) or four DNA duplexes, phi increases as the distance between the duplexes decreases. Combining this result with experimental results for the dependence of the DNA melting temperature on bulk salt concentration, we conclude that for a pair of DNA duplexes the melting temperature increases by 5-10 K for interaxis separations of 25-40 A. For a cluster of four DNA duplexes, an even larger melting temperature increase should occur. We argue that this melting temperature increase in dense DNA clusters is responsible for the cooperative melting mechanism in DNA-linked nanoparticle aggregates and DNA-linked polymer aggregates.     

Reentrant phase behavior of nanoparticle solutions probed by small-angle scattering

The nanoparticles in solution represent a model system, where the well-established colloidal theories such as the Debye–Hückel theory and/or Derjaguin–Landau–Verwey–Overbeek theory can be implemented to predict the nanoparticle phase behavior. Recently, reentrant phase transitions in a wide range of colloids (e.g., inorganic and organic nanoparticles, polymers, and biomolecules) have been observed, which are not consistent with these theories. The colloids in the reentrant phase behavior undergo a phase change and return back to the original phase with respect to a specific physiochemical parameter (e.g., ionic strength, concentration of different additives, temperature, and so on). The nanoparticle–polymer/multivalent ion systems, demonstrating such phase transition and the corresponding phase behavior in terms of interparticle interactions, have been probed by small-angle scattering. It has been shown how the tuning in interparticle interactions using external parameters can lead to reentrant phase behavior and use the nanoparticle aggregation for building nanohybrids. The deviations of the present observations from those of the standard colloidal theories and the anticipated challenges are also discussed.     

Interfacial phase transition of an environmentally responsive elastin biopolymer adsorbed on functionalized gold nanoparticles studied by colloidal surface plasmon resonance

The change in optical properties of colloidal gold upon aggregation has been used to develop an experimentally convenient colorimetric method to study the interfacial phase transition of an elastin-like polypeptide (ELP), a thermally responsive biopolymer. Gold nanoparticles, functionalized with a self-assembled monolayer (SAM) of mercaptoundecanoic acid onto which an ELP was adsorbed, exhibit a characteristic red color due to the surface plasmon resonance (SPR) of individual colloids. Raising the solution temperature from 10 degrees C to 40 degrees C thermally triggered the hydrophilic-to-hydrophobic phase transition of the adsorbed ELP resulting in formation of large aggregates due to interparticle hydrophobic interaction. Formation of large aggregates caused a change in color of the colloidal suspension from red to violet due to coupling of surface plasmons in aggregated colloids. The surface phase transition of the ELP was reversible, as seen from the reversible change in color upon cooling the suspension to 10 degrees C. The formation of colloidal aggregates due to the interfacial phase transition of adsorbed ELP was independently verified by dynamic light scattering of ELP-modified gold colloids as a function of temperature. Colloidal SPR provides a simple and convenient colorimetric method to study the influence of the solution environment, interfacial properties, and grafting method on the transition properties of ELPs and other environmentally responsive polymers at the solid-water interface.     

Interparticle interactions and direct imaging of colloidal phases assembled from microsphere-nanoparticle mixtures

We investigate the interparticle interactions, phase behavior, and structure of microsphere-nanoparticle mixtures that possess high size and charge asymmetry. We employ a novel Monte Carlo simulation scheme to calculate the effective microsphere interactions in suspension, yielding new insight into the origin of the experimentally observed behavior. The initial settling velocity, final sediment density, and three-dimensional structure of colloidal phases assembled from these binary mixtures via gravitational settling of silica microspheres in water and index-matched solutions exhibit a strong compositional dependence. Confocal laser scanning microscopy is used to directly image and quantify their structural evolution during assembly. Below a lower critical nanoparticle volume fraction (phi(nano) < phi(L,C)), the intrinsic van der Waals attraction between microspheres leads to the formation of colloidal gels. These gels exhibit enhanced consolidation as phi(nano) approaches phi(L,C). When phi(nano) exceeds phi(L,C), an effective repulsion arises between microspheres due to the formation of a dynamic nanoparticle halo around the colloids. From this stable fluid phase, the microspheres settle into a crystalline array. Finally, above an upper critical nanoparticle volume fraction (phi(nano) > phi(U,C)), colloidal gels form whose structure becomes more open with increasing nanoparticle concentration due to the emergence of an effective microsphere attraction, whose magnitude exhibits a superlinear dependence on phi(nano).     

Equivalent temperature and specific ion effects in macromolecule-coated colloid interactions

Ensemble total internal reflection microscopy is used to measure reversible temperature- and specific-ion-mediated interaction potentials between macromolecule-coated colloids and surfaces. Potentials are measured between PEO-PPO-PEO (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide)) block copolymers adsorbed to hydrophobically modified silica colloids and glass or gold planar surfaces. Conditions investigated include temperatures from 20 to 47 degrees C and MgSO4 concentrations from 0.2 to 0.5 M. The solvent-quality-mediated copolymer layer collapse inferred by comparing measured potentials and the predicted van der Waals attraction, including effects of the adsorbed copolymer and surface roughness, displays good agreement with expected limits based on the PEO block contour length and the bulk PEO density. Superposition of all PEO layer collapse measurements onto a single universal curve, via a transformed temperature scale relative to a reference temperature in each case, indicates an equivalence of increasing temperature and increasing MgSO4 concentration when layer interactions and dimensions are mediated. Accurate knowledge of nanometer- and kT-scale interactions of copolymer-coated colloids as a function of temperature and MgSO4 concentration provides the ability to reversibly control the stability, phase behavior, and self-assembly of such particles.     

Cationic gel-phase liposomes with "decorated" anionic SPIO nanoparticles: morphology, colloidal, and bilayer properties

The assembly and complexation of oppositely charged colloids are important phenomena in many natural and synthetic processes. Liposome-nanoparticle assemblies (LNAs) represent an interesting hybrid system that combines "soft" and "hard" colloidal materials. This work describes the formation and characterization of gel-phase LNAs formed by the binding of anionic superparamagnetic iron oxide (SPIO) nanoparticles to cationic dipalmitoylphosphatidylcholine (DPPC)/dipalmitoyltrimethylammonium propane (DPTAP) liposomes. Particles were examined with hydrodynamic diameters below (16 nm) and above (30 nm) the cutoff reported for supported lipid bilayer formation. LNA formation with 16 nm particles was entropically driven and particles bound individually to yield "decorated" structures. In this case, increasing nanoparticle concentration yielded colloidal LNA aggregates and eventual charge inversion. In contrast, LNA formation with 30 nm particles was enthalpically driven, and the nanoparticles aggregated at the bilayer interface. These aggregates led to significant LNA aggregation and large bilayer sheets due to liposome rupture despite minimal charge screening of the liposome surface. In this case SLBs were present, but these structures were not dominant. Differences in LNA structure were also revealed through the lipid phase transition behavior. This work infers size-dependent nanoparticle binding and LNA formation mechanisms that can be used to tailor colloidal and bilayer properties. Analogies are made to polyelectrolyte patch charge heterogeneities and DNA complexation with cationic liposomes.     

Phase behavior of polymer/nanoparticle blends near a substrate

We use the recent fluids density functional theory of Tripathi and Chapman [Phys. Rev. Lett. 94, 087801 (2005); J. Chem. Phys. 122, 094506 (2005)] to investigate the phase behavior of athermal polymer/nanoparticle blends near a substrate. The blends are modeled as a mixture of hard spheres and freely jointed hard chains, near a hard wall. There is a first order phase transition present in these blends in which the nanoparticles expel the polymer from the surface to form a monolayer at a certain nanoparticle concentration. The nanoparticle transition density depends on the length of the polymer, the nanoparticle diameter, and the overall bulk density of the system. The phase transition is due to both packing entropy effects related to size asymmetry between the components and to the polymer configurational entropy, justifying the so-called "entropic push" observed in experiments. In addition, a layered state is found at higher densities which resembles that in colloidal crystals, in which the polymer and nanoparticles form alternating discrete layers. We show that this laminar state has nearly the same free energy as the homogeneously mixed fluid in the bulk and is nucleated by the surface.     

Two-dimensional facets in Langmuir monolayers of 1-O-hexadecyl-rac-glycerol at the air-water interface

We study the surface phase behavior in Langmuir monolayers of 1-O-hexadecyl-rac-glycerol (C16G) by film balance and Brewster angle microscopy over a wide range of temperatures. A cusp point followed by a pronounced plateau region in the pressure-area (pi-A) isotherm indicates a first-order phase transition between a lower density liquid expanded (LE) phase and a higher density liquid condensed (LC) phase at the air-water interface. A wide variety of condensed domains are found to form just after the appearance of the cusp point. The observed surface morphology was compared with that of ethylene glycol mono-n-hexadecyl ether (C16E1) that bears an ethylene oxide (EO) unit in the head-group. As usually observed, the domains of C16E1 are found to be circular at lower temperatures and fractal at higher temperatures. Contrary to this usual behavior, the domains of C16G are found to be strip-like structures at lower temperatures, which attain increasingly compact shape as the temperature increases and finally attain faceted structures at > or = 25 degrees C. It is concluded that a higher degree of dehydration around the head-group region of C16G appreciably reduces the hydration-induced repulsive interactions between the head-groups and imparts to the molecules an increase in hydrophobicity, thereby a closer molecular packing. As a result, the molecules form increasingly compact domains as the temperature increases. Since the head-group of C16E1 is much smaller than that of C16G, dehydration effect cannot appreciably increase its hydrophobic character. Rather, increases in subphase temperature result in a decrease in the line tension of the interface giving fractal structures at higher temperatures. In addition, the changes in enthalpy (deltaH) and entropy (deltaS) values were also calculated to understand the thermodynamic nature of condensation of the molecules in the LE-LC transition region.     

Effects of colloidal and dissolved silica on the dissolution of UO2 nuclear fuel in groundwater leaching tests

The influence of aqueous silica of two different physical forms (dissolved ions and SiO₂ colloid) on the dissolution of UO₂ nuclear fuel material was investigated at 95 °C temperature in autoclaves. It was tested that SiO₂ colloids can contribute to the surface degradation or act as carrier for uranium ions during a near field geochemical dissolution process. In the presence of colloids, well-crystallized secondary phases containing U and Si were formed on the surfaces, the latter attacked by the treatment. This was not the case when dissolved Si was used. SiO₂ colloids were partly found in their original form on the surfaces after 1000 hours at 95 °C. A surface charge model suggests that this different effects are due to the development of electrostatic interactions between the UO₂ and SiO₂ surfaces.This revised version was published online in November 2005 with corrections to the Cover Date.     

Temperature-responsive formation of colloidal nanoparticles from poly(N-isopropylacrylamide) grafted with single-stranded DNA

The thermal properties and temperature-responsive nanoparticle formation of poly(N-isopropylacrylamide) grafted with single-stranded DNA (PNIPAAm-g-DNA) were investigated. Copolymerization between nonamer single-stranded DNA with a vinyl group at its 5' terminus (DNA macromonomer) and NIPAAm was carried out so that the DNA macromonomer unit content should be less than 1 mol %. The turbidimetry and differential scanning calorimetry of the copolymer showed that the transition temperature increased and the enthalpy change of the phase transition decreased with increasing DNA macromonomer content in the copolymers, indicating that the DNA macromonomer behaves as a hydrophilic part in the copolymer and that the hydrophilicity is greater than that of sodium styrenesulfonate. Above the phase transition temperature, the copolymers formed colloidal nanoparticles with a dehydrated PNIPAAm core surrounded by DNA. When the formation of particles was conducted at higher temperatures, the dehydration of the copolymers proceeded such that the hydrodynamic radius (Rh) of the particles decreased. From the results of light scattering measurements, we calculated the surface area of particles occupied by one DNA (S(DNA)). The S(DNA) value decreased with increasing formation temperature, indicating that the DNA density on the particle surface increases with increasing formation temperature. The increase in the DNA density was also confirmed from the zeta-potential measurement of the particle. When MgCl2 was added to the copolymer solutions, the anionic charge of DNA was neutralized by Mg2+ so that Rh and the molecular weight of the particles increased with the increasing MgCl2 concentration. The turbidimetric detection of a target DNA was successfully demonstrated by utilizing the stability decrease of the colloidal particle upon hybridization on the particle surface.     

Melting and mechanical properties of polymer grafted lipid bilayer membranes

The influence of polymer grafting on the phase behavior and elastic properties of two tail lipid bilayers have been investigated using dissipative particle dynamics simulations. For the range of polymer lengths studied, the L(c) to L(α) transition temperature is not significantly affected for grafting fractions, G(f) between 0.16 and 0.25. A decrease in the transition temperature is observed at a relatively high grafting fraction, G(f) = 0.36. At low temperatures, a small increase in the area per head group, a(h), at high G(f) leads to an increase in the chain tilt, inducing order in the bilayer and the solvent. The onset of the phase transition occurs with the nucleation of small patches of thinned membrane which grow and form continuous domains as the temperature increases. This region is the co-existence region between the L(β)(thick) and the L(α)(thin) phases. The simulation results for the membrane area expansion as a function of the grafting density conform extremely well to the scalings predicted by self-consistent mean field theories. We find that the bending modulus shows a small decrease for short polymers (number of beads, N(p) = 10) and low G(f), where the influence of polymer is reduced when compared to the effect of the increased a(h). For longer polymers (N(p) > 15), the bending modulus increases monotonically with increase in grafted polymer. Using the results from mean field theory, we partition the contributions to the bending modulus from the membrane and the polymer and show that the dominant contribution to the increased bending modulus arises from the grafted polymer.     

Behavior of thermosensitive graft copolymer with aromatic polyester backbone and poly-2-ethyl-2-oxazoline side chains in aqueous solutions

Thermoresponsive graft copolymers with alkylene-aromatic polyester main chain and poly-2-ethyl-2-oxazoline side chains were synthesized. Two copolymer samples which differed in grafting density (0.5 and 0.7) were studied using dynamic and static light scattering and turbidimetry in aqueous solutions at concentration 0.0053?g?cm^?3. Hydrodynamic radii of scattering objects and their contribution to light scattering were obtained as a function of temperature in a wide temperature interval. Temperatures of phase separation were found out. Effect of grafting density on the copolymer behavior in aqueous solutions upon heating was determined. In particular, the phase separation temperature reduces with the decreasing grafting density.     

PNIPAM chain collapse depends on the molecular weight and grafting density

This study demonstrates that the thermally induced collapse of end-grafted poly(N-isopropylacrylamide) (PNIPAM) above the lower critical solution temperature (LCST) of 32 degrees C depends on the chain grafting density and molecular weight. The polymer was grafted from the surface of a self-assembled monolayer containing the initiator (BrC(CH3)2COO(CH2)11S)2, using surface-initiated atom transfer radical polymerization. Varying the reaction time and monomer concentration controlled the molecular weight, and diluting the initiator in the monolayer altered the grafting density. Surface force measurements of the polymer films showed that the chain collapse above the LCST decreases with decreasing grafting density and molecular weight. At T > LCST, the advancing water contact angle increases sharply on PNIPAM films of high molecular weight and grafting density, but the change is less pronounced with films of low-molecular-weight chains at lower densities. Below the LCST, the force-distance profiles exhibit nonideal polymer behavior and suggest that the brush architecture comprises dilute outer chains and much denser chains adjacent to the surface.     

Collapse and shedding transitions in binary lipid monolayers coating microbubbles

We report on a fluorescence microscopy study of the monolayer collapse and shedding behavior due to shell compression during the dissolution of air-filled, lipid-coated microbubbles in degassed media. The monolayer shell was comprised of saturated diacyl phosphatidylcholine (C12:0 to C22:0) and an emulsifier, poly(ethylene glycol)-40 stearate. The morphologies of monolayer collapse structures and shed particles were monitored as a function of phospholipid acyl chain length (n) and temperature. The two components formed a single miscible phase when the phospholipid was near or above its main phase transition temperature, and collapse occurred via suboptical particles to vesicles (both were shed) and tubes as chain length increased. Conversely, two-phase coexistence was observed when the lipid was below its main phase transition temperature. For these bubbles, a transition from primary collapse to secondary collapse was observed. Primary collapse was observed as a loss of expanded phase due to vesiculation. Secondary collapse involved the rapid propagation of monolayer folds and simultaneous deformation. For very rigid monolayers, we observed substantial surface buckling with simultaneous nucleation and growth of folds. The folds merged at a single point or region, providing a conduit for the entire excess lipid to shed in a single event, and the bubble smoothed and became more spherical. These results are discussed in the context of general binary phospholipid collapse behavior, microbubble dissolution behavior, medical applications, and the dissolution behavior of natural microbubbles.