DNA-coated Colloids Research Articles

Hopping and crawling DNA-coated colloids

Understanding the motion of particles with multivalent ligand-receptors is important for biomedical applications and material design. Yet, even among a single design, the prototypical DNA-coated colloids, seemingly similar micrometric particles hop or roll, depending on the study. We shed light on this problem by observing DNA-coated colloids diffusing near surfaces coated with complementary strands for a wide array of coating designs. We find colloids rapidly switch between 2 modes: They hop-with long and fast steps-and crawl-with short and slow steps. Both modes occur at all temperatures around the melting point and over various designs. The particles become increasingly subdiffusive as temperature decreases, in line with subsequent velocity steps becoming increasingly anticorrelated, corresponding to switchbacks in the trajectories. Overall, crawling (or hopping) phases are more predominant at low (or high) temperatures; crawling is also more efficient at low temperatures than hopping to cover large distances. We rationalize this behavior within a simple model: At lower temperatures, the number of bound strands increases, and detachment of all bonds is unlikely, hence, hopping is prevented and crawling favored. We thus reveal the mechanism behind a common design rule relying on increased strand density for long-range self-assembly: Dense strands on surfaces are required to enable crawling, possibly facilitating particle rearrangements.

DNA-Based Replication of Programmable Colloidal Assemblies.

Nature uses replication to amplify the information necessary for the intricate structures vital for life. Despite some successes with pure nucleotide structures, constructing synthetic microscale systems capable of replication remains largely out of reach. Here, a functioning strategy is shown for the replication of microscale particle assemblies using DNA-coated colloids. By positioning DNA-functionalized colloids using capillary forces and embedding them into a polymer layer, programmable sequences of patchy particles are created that act as a primer and offer precise binding of complementary particles from suspension. The strings of complementary colloids are cross-linked, released from the primer, and purified via flow cytometric sorting to achieve a purity of up to 81% of the replicated sequences. The replication of strings of up to five colloids and non-linear shapes is demonstrated with particles of different sizes and materials. Furthermore, a pathway for exponential self-replication is outlined, including preliminary data that shows the transfer of patches and binding of a second-generation of assemblies fromsuspension.

Nonequilibrium design strategies for functional colloidal assemblies

We use a nonequilibrium variational principle to optimize the steady-state, shear-induced interconversion of self-assembled nanoclusters of DNA-coated colloids. Employing this principle within a stochastic optimization algorithm allows us to identify design strategies for functional materials. We find that far-from-equilibrium shear flow can significantly enhance the flux between specific colloidal states by decoupling trade-offs between stability and reactivity required by systems in equilibrium. For isolated nanoclusters, we find nonequilibrium strategies for amplifying transition rates by coupling a given reaction coordinate to the background shear flow. We also find that shear flow can be made to selectively break detailed balance and maximize probability currents by coupling orientational degrees of freedom to conformational transitions. For a microphase consisting of many nanoclusters, we study the flux of colloids hopping between clusters. We find that a shear flow can amplify the flux without a proportional compromise on the microphase structure. This approach provides a general means of uncovering design principles for nanoscale, autonomous, functional materials driven far from equilibrium.

Whole-genome detection using multivalent DNA-coated colloids

To minimize the incorrect use of antibiotics, there is a great need for rapid and inexpensive tests to identify the pathogens that cause an infection. The gold standard of pathogen identification is based on the recognition of DNA sequences that are unique for a given pathogen. Here, we propose and test a strategy to develop simple, fast, and highly sensitive biosensors that make use of multivalency. Our approach uses DNA-functionalized polystyrene colloids that distinguish pathogens on the basis of the frequency of selected short DNA sequences in their genome. Importantly, our method uses entire genomes and does not require nucleic acid amplification. Polystyrene colloids grafted with specially designed surface DNA probes can bind cooperatively to frequently repeated sequences along the entire genome of the target bacteria, resulting in the formation of large and easily detectable colloidal aggregates. Our detection strategy allows "mix and read" detection of the target analyte; it is robust and highly sensitive over a wide concentration range covering, in the case of our test target genome Escherichia coli bl21-de3, 10 orders of magnitude from [Formula: see text] to [Formula: see text] copies/mL. The sensitivity compares well with state-of-the-art sensing techniques and has excellent specificity against nontarget bacteria. When applied to real samples, the proposed technique shows an excellent recovery rate. Our detection strategy opens the way to developing a robust platform for pathogen detection in the fields of food safety, disease control, and environmental monitoring.

Ordered stripes to crack patterns in dried particulates of DNA-coated gold colloids via modulating nanoparticle-substrate interactions.

The surface pattern in dried droplets of nanoparticle suspension possesses direct correlation with the evaporation profile, which apart from the bulk parameters, can also be altered by tuning the nanoscale interactions. Here, we show that, for sessile drops of DNA-coated gold nanoparticle (DNA-AuNP) solution, the alteration in evaporation pathway of TPCL (three-phase contact line) from stick-slip to mixed mode leads to a surface morphological transition from concentric rings with stripes to radial crack formation within the coffee ring deposit. A freshly cleaned silicon substrate offers hydrophilic/favorable substrate-nanoparticle interaction and produces multiple ordered stripes due to stick-slip motion of the TPCL. Using a SiO2/Si substrate with ∼200 nm of oxide layer leads to an increase in the initial water contact angle θi-w by ∼40°, due to increased hydrophobicity of the substrate. Three distinct modes of evaporation are observed - constant contact radius (CCR), constant contact angle (CCA) and mixed mode, resulting in the formation of radial cracks on a thick coffee ring structure. The critical thickness (hc), beyond which the cracks start to appear, was measured to be ∼600 nm and is in close agreement with the theoretical estimate of ∼510 nm. Through in situ contact angle and ex situ SEM measurements, we provide an understanding of the observed surface morphological transition in the dried particulate at various nanoparticle densities. Further analysis of the coffee ring width (d), linear crack density (σ) and crack spacing (λ) provides insight into the mechanism of crack formation for droplets dried on oxide-coated substrates.

A simple method to alter the binding specificity of DNA-coated colloids that crystallize.

DNA-coated colloids can crystallize into a multitude of lattices, ranging from face-centered cubic to diamond, opening avenues to producing structures with useful photonic properties. The potential design space of DNA-coated colloids is large, but its exploration is hampered by a reliance on chemically modified DNA that is slow and expensive to commercially synthesize. Here we introduce a method to controllably tailor the sequences of DNA-coated particles by covalently appending new sequence domains onto the DNA grafted to colloidal particles. The tailored particles crystallize as readily and at the same temperature as those produced via direct chemical synthesis, making them suitable for self-assembly. Moreover, we show that particles coated with a single sequence can be converted into a variety of building blocks with differing specificities by appending different DNA sequences to them. This method will make it practical to identify optimal and complex particle sequence designs and paves the way to programming the assembly kinetics of DNA-coated colloids.

Staged Assembly of Colloids Using DNA and Acoustofluidics.

Assembly of DNA-coated colloids (DNACCs) provides a practical route to programming complex self-assembled materials at the micro/nanoscale. So far, the programmability of DNACC assembly has been extensively exploited internally using different DNA sequences or colloid geometry so that the assembly is mainly manipulated with single-particle spatial resolution such as in crystallization. In this Letter, we present an acoustic approach to externally programming the DNACC assembly with control of spatial resolution over larger scales. We demonstrate assembly of the DNACCs under different acoustic frequencies from stage to stage to produce hierarchical structures that are difficult to fabricate when using DNA coating alone. By programming the acoustic wave frequency, amplitude, and phase, colloidal structures with different morphologies can be assembled. The nonspecific driving force based on acoustic radiation forces at each stage allows our approach to be adopted for most colloidal systems without specific requirements on particle or medium properties.

Mass Changes the Diffusion Coefficient of Particles with Ligand-Receptor Contacts in the Overdamped Limit.

Inertia does not generally affect the long-time diffusion of passive overdamped particles in fluids. Yet a model starting from the Langevin equation predicts a surprising property of particles coated with ligands that bind reversibly to surface receptors: heavy particles diffuse more slowly than light ones of the same size. We show this by simulation and by deriving an analytic formula for the mass-dependent diffusion coefficient in the overdamped limit. We estimate the magnitude of this effect for a range of biophysical ligand-receptor systems, and find it is potentially observable for tailored micronscale DNA-coated colloids.

Comprehensive view of microscopic interactions between DNA-coated colloids

The self-assembly of DNA-coated colloids into highly-ordered structures offers great promise for advanced optical materials. However, control of disorder, defects, melting, and crystal growth is hindered by the lack of a microscopic understanding of DNA-mediated colloidal interactions. Here we use total internal reflection microscopy to measure in situ the interaction potential between DNA-coated colloids with nanometer resolution and the macroscopic melting behavior. The range and strength of the interaction are measured and linked to key material design parameters, including DNA sequence, polymer length, grafting density, and complementary fraction. We present a first-principles model that screens and combines existing theories into one coherent framework and quantitatively reproduces our experimental data without fitting parameters over a wide range of DNA ligand designs. Our theory identifies a subtle competition between DNA binding and steric repulsion and accurately predicts adhesion and melting at a molecular level. Combining experimental and theoretical results, our work provides a quantitative and predictive approach for guiding material design with DNA-nanotechnology and can be further extended to a diversity of colloidal and biological systems.

The nanocaterpillar's random walk: diffusion with ligand-receptor contacts.

Particles with ligand-receptor contacts bind and unbind fluctuating "legs" to surfaces, whose fluctuations cause the particle to diffuse. Quantifying the diffusion of such "nanoscale caterpillars" is a challenge, since binding events often occur on very short time and length scales. Here we derive an analytical formula, validated by simulations, for the long time translational diffusion coefficient of an overdamped nanocaterpillar, under a range of modeling assumptions. We demonstrate that the effective diffusion coefficient, which depends on the microscopic parameters governing the legs, can be orders of magnitude smaller than the background diffusion coefficient. Furthermore it varies rapidly with temperature, and reproduces the striking variations seen in existing data and our own measurements of the diffusion of DNA-coated colloids. Our model gives insight into the mechanism of motion, and allows us to ask: when does a nanocaterpillar prefer to move by sliding, where one leg is always linked to the surface, and when does it prefer to move by hopping, which requires all legs to unbind simultaneously? We compare a range of systems (viruses, molecular motors, white blood cells, protein cargos in the nuclear pore complex, bacteria such as Escherichia coli, and DNA-coated colloids) and present guidelines to control the mode of motion for materials design.

Self-assembly of photonic crystals by controlling the nucleation and growth of DNA-coated colloids

DNA-coated colloids can self-assemble into an incredible diversity of crystal structures, but their applications have been limited by poor understanding and control over the crystallization dynamics. To address this challenge, we use microfluidics to quantify the kinetics of DNA-programmed self-assembly along the entire crystallization pathway, from thermally activated nucleation through reaction-limited and diffusion-limited phases of crystal growth. Our detailed measurements of the temperature and concentration dependence of the kinetics at all stages of crystallization provide a stringent test of classical theories of nucleation and growth. After accounting for the finite rolling and sliding rates of micrometer-sized DNA-coated colloids, we show that modified versions of these classical theories predict the absolute nucleation and growth rates with quantitative accuracy. We conclude by applying our model to design and demonstrate protocols for assembling large single crystals with pronounced structural coloration, an essential step in creating next-generation optical metamaterials from colloids.

Programming Self-Assembled Materials With DNA-Coated Colloids

Introducing the concept of programmability paves the way for designing complex and intelligent materials, where the materials’ structural information is pre-encoded in the components that build the system. With highly tunable interactions, DNA-coated particles are promising building elements to program materials at the colloidal scale, but several grand challenges have prevented them from assembling into the desired structures and phases. In recent years, the field has seen significant progress in tackling these challenges, which has led to the realization of numerous colloidal structures and dynamics previously inaccessible, including the desirable colloidal diamond structure, that are useful for photonic and various other applications. We review this exciting progress, focusing in detail on how DNA-coated colloids can be designed to have a sophisticatedly tailored surface, shape, patches, as well as controlled kinetics, which are key factors that allow one to program in principle a limitless number of structures. We also share our view on how the field may be directed in future.

Two-step crystallization and solid–solid transitions in binary colloidal mixtures

Crystallization is fundamental to materials science and is central to a variety of applications, ranging from the fabrication of silicon wafers for microelectronics to the determination of protein structures. The basic picture is that a crystal nucleates from a homogeneous fluid by a spontaneous fluctuation that kicks the system over a single free-energy barrier. However, it is becoming apparent that nucleation is often more complicated than this simple picture and, instead, can proceed via multiple transformations of metastable structures along the pathway to the thermodynamic minimum. In this article, we observe, characterize, and model crystallization pathways using DNA-coated colloids. We use optical microscopy to investigate the crystallization of a binary colloidal mixture with single-particle resolution. We observe classical one-step pathways and nonclassical two-step pathways that proceed via a solid-solid transformation of a crystal intermediate. We also use enhanced sampling to compute the free-energy landscapes corresponding to our experiments and show that both one- and two-step pathways are driven by thermodynamics alone. Specifically, the two-step solid-solid transition is governed by a competition between two different crystal phases with free energies that depend on the crystal size. These results extend our understanding of available pathways to crystallization, by showing that size-dependent thermodynamic forces can produce pathways with multiple crystal phases that interconvert without free-energy barriers and could provide approaches to controlling the self-assembly of materials made from colloids.

Reconfigurable Transitions between One- and Two-Dimensional Structures with Bifunctional DNA-Coated Janus Colloids.

Coating colloidal particles with DNA provides one of the most versatile and powerful methods for controlling colloidal self-assembly. Previous studies have shown how combining DNA coatings with DNA strand displacement allows one to design phase transitions between different three-dimensional crystal structures. Here we show that by using DNA coatings with bifunctional colloidal Janus particles, we can realize reconfigurable thermally reversible transitions between one- and two-dimensional self-assembled colloidal structures. We introduce a colloidal system in which DNA-coated asymmetric Janus particles can reversibly switch their Janus balance in response to temperature, resulting in the reconfiguration of assembling structures between colloidal chains and bilayers. Each face of the Janus particles is coated with different self-complementary DNA strands. Toehold strand displacement is employed to selectively activate or deactivate the sticky ends on the smaller face, which enables Janus particles to selectively assemble through either the smaller or larger face. This strategy could be useful for constructing complex systems that could be reconfigured to assemble into different structures in different environments.

A mean-field model of linker-mediated colloidal interactions.

Programmable self-assembly is one of the most promising strategies for making ensembles of nanostructures from synthetic components. Yet, predicting the phase behavior that emerges from a complex mixture of many interacting species is difficult, and designing such a system to exhibit a prescribed behavior is even more challenging. In this article, I develop a mean-field model for predicting linker-mediated interactions between DNA-coated colloids, in which the interactions are encoded in DNA molecules dispersed in solution instead of in molecules grafted to particles' surfaces. As I show, encoding interactions in the sequences of free DNA oligomers leads to new behavior, such as a re-entrant melting transition and a temperature-independent binding free energy per kBT. This unique phase behavior results from a per-bridge binding free energy that is a nonlinear function of the temperature and a nonmonotonic function of the linker concentration, owing to subtle entropic contributions. To facilitate the design of experiments, I also develop two scaling limits of the full model that can be used to select the DNA sequences and linker concentrations needed to program a specific behavior or favor the formation of a prescribed target structure. These results could ultimately enable the programming and tuning of hundreds of mutual interactions by designing cocktails of linker sequences, thus pushing the field toward the original goal of programmable self-assembly: these user-prescribed structures can be assembled from complex mixtures of building blocks through the rational design of their interactions.

Linker-mediated self-assembly of mobile DNA-coated colloids.

Developing construction methods of materials tailored for given applications with absolute control over building block placement poses an immense challenge. DNA-coated colloids offer the possibility of realising programmable self-assembly, which, in principle, can assemble almost any structure in equilibrium, but remains challenging experimentally. Here, we propose an innovative system of linker-mediated mobile DNA-coated colloids (mDNACCs), in which mDNACCs are bridged by the free DNA linkers in solution, whose two single-stranded DNA tails can bind with specific single-stranded DNA receptors of complementary sequence coated on colloids. We formulate a mean-field theory efficiently calculating the effective interaction between mDNACCs, where the entropy of DNA linkers plays a nontrivial role. Particularly, when the binding between free DNA linkers in solution and the corresponding receptors on mDNACCs is strong, the linker-mediated colloidal interaction is determined by the linker entropy depending on the linker concentration.

Self-Assembly and Crystallization of DNA-Coated Colloids via Linker-Encoded Interactions.

Coating colloidal particles with DNA is a promising strategy to make functional nanoscale materials because the particles can be programmed to spontaneously self-assemble into complex, ordered structures. In this Article, we explore the phase behavior and types of structures that can be formed when interactions between DNA-coated colloids are specified by linker DNA strands dispersed in solution. We show that linker-mediated interactions direct the self-assembly of colloids into equilibrium crystal structures. Furthermore, we demonstrate how different linker sequences and concentrations produce different crystal lattices, whose symmetry and compositional order are encoded exclusively by the linker-mediated interactions. These results illustrate how linkers can be used to separate the assembly instructions, encoded in the linkers, from the colloids themselves. We also examine the phase behavior of asymmetric linkers, which bind more strongly to one colloidal species than the other. We find that asymmetry strongly influences the concentration dependence of the colloidal interactions, which we explain using a mean-field model. We also find evidence that asymmetric linkers might help to reduce kinetic bottlenecks to colloidal crystallization. Together, our findings expand the design rules of linker-mediated self-assembly and make connections between the various schemes for programming assembly of DNA-coated colloids reported in the literature.

Linker-Mediated Phase Behavior of DNA-Coated Colloids

The possibility of prescribing local interactions between nano- and microscopic components that direct them to assemble in a predictable fashion is a central goal of nanotechnology research. In this article, we advance a new paradigm in which the self-assembly of DNA-functionalized colloidal particles is programmed using linker oligonucleotides dispersed in solution. We find a phase diagram that is surprisingly rich compared to phase diagrams typical of other DNA-functionalized colloidal particles that interact by direct hybridization, including a reentrant melting transition upon increasing linker concentration, and show that multiple linker species can be combined to prescribe many interactions simultaneously. A new theory predicts the observed phase behavior quantitatively without any fitting parameters. Taken together, these experiments and model lay the groundwork for future research in programmable self-assembly, enabling the possibility of programming the hundreds of specific interactions needed to assemble fully addressable, mesoscopic structures, while also expanding our fundamental understanding of the unique phase behavior possible in colloidal suspensions.Received 14 March 2019Revised 13 August 2019DOI:https://doi.org/10.1103/PhysRevX.9.041054Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.Published by the American Physical SocietyPhysics Subject Headings (PhySH)Research AreasClassical statistical mechanicsPhase behaviorPhase diagramsSelf-assemblyPhysical SystemsColloidsDNAStatistical PhysicsCondensed Matter, Materials & Applied PhysicsPolymers & Soft Matter

DNA functionalization of colloidal particles via physisorption of azide-functionalized diblock copolymers.

DNA-coated inorganic particles can be prepared simply by physical adsorption of azide-functionalized diblock copolymers (polystyrene-b-poly(ethylene oxide)-azide, PS-b-PEO-N3) onto hydrophobically-modified inorganic particles, followed by strain-promoted azide-alkyne cycloaddition (SPAAC, copper-free click chemistry). This approach is applied to organosilica, silica and titania particles. The DNA-coated colloids are successfully crystallized into colloidal superstructures by a thermal annealing process using DNA-mediated assembly.

Entropy Stabilizes Floppy Crystals of Mobile DNA-Coated Colloids.

Grafting linkers with open ends of complementary single-stranded DNA makes a flexible tool to tune interactions between colloids, which facilitates the design of complex self-assembly structures. Recently, it has been proposed to coat colloids with mobile DNA linkers, which alleviates kinetic barriers without high-density grafting, and also allows the design of valency without patches. However, the self-assembly mechanism of this novel system is poorly understood. Using a combination of theory and simulation, we obtain phase diagrams for the system in both two and three dimensional spaces, and find stable floppy square and CsCl crystals when the binding strength is strong, even in the infinite binding strength limit. We demonstrate that these floppy phases are stabilized by vibrational entropy, and "floppy" modes play an important role in stabilizing the floppy phases for the infinite binding strength limit. This special entropic effect in the self-assembly of mobile DNA-coated colloids is very different from conventional molecular self-assembly, and it offers a new axis to help design novel functional materials using mobile DNA-coated colloids.