DNA and colloids

Short, custom-designed DNA molecules can be used to create "programmable" interactions between colloidal particles, meaning that we can control how the particles self-assemble through the DNA sequences. Currently we are trying to create colloids with programmable dynamic behavior. Using DNA, we make colloidal "motors" that move in a directed (non-random) way and colloidal suspensions that organize into patterns that change with time.

Publications

Garmann, R. F. ; Sportsman, R. ; Beren, C. ; Manoharan, V. N. ; Knobler, C. M. ; Gelbart, W. M. A Simple RNA-DNA Scaffold Templates the Assembly of Monofunctional Virus-Like Particles. JACS 2015, 137, 7584–7587. Publisher's VersionAbstract

Using the components of a particularly well-studied plant virus, cowpea chlorotic mottle virus (CCMV), we demonstrate the synthesis of virus-like particles (VLPs) with one end of the packaged RNA extending out of the capsid and into the surrounding solution. This construct breaks the otherwise perfect symmetry of the capsid and provides a straightforward route for monofunctionalizing VLPs using the principles of DNA nanotechnology. It also allows physical manipulation of the packaged RNA, a previously inaccessible part of the viral architecture. Our synthesis does not involve covalent chemistry of any kind; rather, we trigger capsid assembly on a scaffold of viral RNA that is hybridized at one end to a complementary DNA strand. Interaction of CCMV capsid protein with this RNA-DNA template leads to selective packaging of the RNA portion into a well-formed capsid but leaves the hybridized portion poking out of the capsid through a small hole. We show that the nucleic acid protruding from the capsid is capable of binding free DNA strands and DNA-functionalized colloidal particles. Separately, we show that the RNA-DNA scaffold can be used to nucleate virus formation on a DNA-functionalized surface. We believe this self-assembly strategy can be adapted to viruses other than CCMV.

Schade, N. B. Self-Assembly of Plasmonic Nanoclusters for Optical Metafluids, 2015. Publisher's VersionAbstract

I discuss experimental progress towards developing a material with an isotropic, negative index of refraction at optical frequencies. The simplest way to make such a material is to create a metafluid, or a disordered collection of subwavelength, isotropic electromagnetic resonators. Small clusters of metal particles, such as tetrahedra, serve as these constituents. What is needed are methods for manufacturing these structures with high precision and in sufficient yield that their resonances are identical.

Jonathan Fan et al. [Science, 328 (5982), 1135-1138, 2010] demonstrated that colloidal self-assembly is a means of preparing electromagnetic resonators from metal nanoparticles. However, the resonances are sensitive to the separation gaps between particles. Standard synthesis routes for metal nanoparticles yield crystals or nanoshells that are inadequate for metafluids due to polydispersity, faceting, and thermal instabilities. To ensure that the separation gaps and resonances are uniform, more monodisperse spherical particles are needed. An additional challenge is the self-assembly of tetrahedral clusters in high yield from these particles. In self-assembly approaches that others have examined previously, the yield of any particular type of cluster is low.

In this dissertation I present solutions to several of these problems, developed in collaboration with my research group and others. We demonstrate that slow chemical etching can transform octahedral gold crystals into ultrasmooth, monodisperse nanospheres. The particles can serve as seeds for the growth of larger octahedra which can in turn be etched. The size of the gold nanospheres can therefore be adjusted as desired. We further show that in colloidal mixtures of two sphere species that strongly bind to one another, the sphere size ratio determines the size distribution of self-assembled clusters. At a critical size ratio, tetrahedral clusters assemble in high yield. We explain the experimentally observed 90% yield with a nonequilibrium “random parking” model based on irreversible binding. Simulations based on this model reveal that 100% yield of tetrahedra is possible in principle. Finally, we combine these results and present methods for the self-assembly and purification of tetrahedral plasmonic nanoclusters, the simplest building blocks for isotropic metafluids.

Rogers, W. B. ; Manoharan, V. N. Programming colloidal phase transitions with DNA strand displacement. Science 2015, 347, 639-642. Publisher's VersionAbstract

DNA-grafted nanoparticles have been called “programmable atom-equivalents”: Like atoms, they form three-dimensional crystals, but unlike atoms, the particles themselves carry information (the sequences of the grafted strands) that can be used to “program” the equilibrium crystal structures. We show that the programmability of these colloids can be generalized to the full temperature-dependent phase diagram, not just the crystal structures themselves. We add information to the buffer in the form of soluble DNA strands designed to compete with the grafted strands through strand displacement. Using only two displacement reactions, we program phase behavior not found in atomic systems or other DNA-grafted colloids, including arbitrarily wide gas-solid coexistence, reentrant melting, and even reversible transitions between distinct crystal phases.

Collins, J. W. Self-Assembly of Colloidal Spheres with Specific Interactions, 2014. Publisher's VersionAbstract

In this thesis, I discuss engineering colloidal particles to have specific, isotropic interactions and studying their cluster geometries in equilibrium. I discuss light scattering experiments showing that a highly specific protein, Dscam, is unstable against thermal aggregation. This result lead me to use DNA instead to control interparticle specificity. I coated 1-micron diameter polystyrene particles uniformly with DNA. I used fluorescence microscopy with oxygen-scavenging enzymes to observe these particles self-assembling in clusters. These experiments show that a packing of 6 spheres that is rarely seen in a single-component system is observed very often in an optimized 3-species system. Then I show experiments using the same 3 species but 9 total particles, finding that the equilibrium yields of the most likely cluster relative to other stable clusters are lower than at 6 particles. I conclude from these experiments that optimizing the assembly of an otherwise unlikely configuration may require nearly as many species as particles. Finally, I investigate the scalability of self-assembly of particles with isotropic and specific interactions theoretically. I use both exact and approximate partition functions to show that spheres with specific interactions can have energy landscapes with thermodynamically large numbers of strictly local minima relative to the number of their ground states. Compared to single-component systems, these systems of many different species may spend much more time in kinetic traps and never reach their ground states. Finally, I discuss briefly some directions for further study, including questions of how the results in this thesis may be related to protein folding and complex formation.

Schade, N. B. ; Holmes-Cerfon, M. C. ; Chen, E. R. ; Aronzon, D. ; Collins, J. W. ; Fan, J. A. ; Capasso, F. ; Manoharan, V. N. Tetrahedral colloidal clusters from random parking of bidisperse spheres . Physical Review Letters 2013, 110, 148303. Publisher's VersionAbstract

Using experiments and simulations, we investigate the clusters that form when colloidal spheres stick irreversibly to—or “park” on—smaller spheres. We use either oppositely charged particles or particles labeled with complementary DNA sequences, and we vary the ratio α of large to small sphere radii. Once bound, the large spheres cannot rearrange, and thus the clusters do not form dense or symmetric packings. Nevertheless, this stochastic aggregation process yields a remarkably narrow distribution of clusters with nearly 90% tetrahedra at α=2.45. The high yield of tetrahedra, which reaches 100% in simulations at α=2.41, arises not simply because of packing constraints, but also because of the existence of a long-time lower bound that we call the “minimum parking” number. We derive this lower bound from solutions to the classic mathematical problem of spherical covering, and we show that there is a critical size ratio αc=(1+√2)≈2.41, close to the observed point of maximum yield, where the lower bound equals the upper bound set by packing constraints. The emergence of a critical value in a random aggregation process offers a robust method to assemble uniform clusters for a variety of applications, including metamaterials.

Wang, Y. ; Wang, Y. ; Breed, D. R. ; Manoharan, V. N. ; Feng, L. ; Hollingsworth, A. D. ; Weck, M. ; Pine, D. J. Colloids with valence and specific directional bonding . Nature 2012, 491, 51-55. Publisher's VersionAbstract

The ability to design and assemble three-dimensional structures from colloidal particles is limited by the absence of specific directional bonds. As a result, complex or low-coordination structures, common in atomic and molecular systems, are rare in the colloidal domain. Here we demonstrate a general method for creating the colloidal analogues of atoms with valence: colloidal particles with chemically distinct surface patches that imitate hybridized atomic orbitals, including sp, sp2, sp3, sp3d, sp3d2 and sp3d3. Functionalized with DNA with single-stranded sticky ends, patches on different particles can form highly directional bonds through programmable, specific and reversible DNA hybridization. These features allow the particles to self-assemble into |[lsquo]|colloidal molecules|[rsquo]| with triangular, tetrahedral and other bonding symmetries, and should also give access to a rich variety of new microstructured colloidal materials.

Fan, J. A. ; He, Y. ; Bao, K. ; Wu, C. ; Bao, J. ; Schade, N. B. ; Manoharan, V. N. ; Shvets, G. ; Nordlander, P. ; Liu, D. R. ; et al. DNA-Enabled Self-Assembly of Plasmonic Nanoclusters. Nano Letters 2011, 11, 4859-4864. Publisher's VersionAbstract

DNA nanotechnology provides a versatile foundation for the chemical assembly of nanostructures. Plasmonic nanoparticle assemblies are of particular interest because they can be tailored to exhibit a broad range of electromagnetic phenomena. In this Letter, we report the assembly of DNA-functionalized nanoparticles into heteropentamer clusters, which consist of a smaller gold sphere surrounded by a ring of four larger spheres. Magnetic and Fano-like resonances are observed in individual clusters. The DNA plays a dual role: it selectively assembles the clusters in solution and functions as an insulating spacer between the conductive nanoparticles. These particle assemblies can be generalized to a new class of DNA-enabled plasmonic heterostructures that comprise various active and passive materials and other forms of DNA scaffolding.