This work reports a valence-centric strategy that enables DNA-bonded, protein single crystals with unconventional mechanical properties and establishes a programmable framework for biomolecular crystallization and nanomaterials engineering with atomic precision.
Abstract
DNA-functionalized colloidal nanoparticles assemble through flexible, nanoscale DNA hybridization interactions that limit atomic-level structural order. Here, we report a valence-centric strategy that enables DNA-bonded, protein single crystals with unconventional mechanical properties. An octameric enzyme, glutarate L-2-hydroxylase, was site- and number-selectively conjugated with eight self-complementary single-stranded DNA, yielding octavalent molecular bonds. The resulting conjugate assembled into the designed body-centered tetragonal crystals that diffracted to 1.42- to 2.61-angstrom resolution, with contacts mediated by B-form DNA helices spanning 17 to 25 angstroms. Increasing oligonucleotide length induces anisotropic lattice expansion while preserving atomic periodicity, even with partial DNA occupancy. Mechanistic studies suggest that the dynamic motion of unhybridized DNA facilitates crystallization, analogous to fluctuating electron clouds in atomic bonding. Compared with native protein crystals, DNA-hybridized crystals are 23-fold softer. These results challenge the assumption that flexibility is incompatible with structural order and establish a programmable framework for biomolecular crystallization and nanomaterials engineering with atomic precision.
Perylenediimide (PDI) and its derivatives are widely studied for their photophysical and photochemical properties, making them promising candidates for photonic materials, organic semiconductors, and molecular qubits. However, the lack of control over their aggregation pathways and charge-transfer coupling severely limits their uses. Here, we report the synthesis of PDI-DNA bioconjugates as a new class of "programmable atom equivalents" (PAEs), in which a single PDI core is covalently linked to two DNA strands. Unlike conventional PAE superlattices formed by slow thermal annealing, the vapor-diffusion crystallization method enables the colloidal crystallization of PDI-DNA conjugates into large single-crystalline superlattices through cooperative DNA hybridization and PDI π-π stacking. The peripheral four sticky ends hybridize into a DNA framework, which serves as a scaffold, organizing the PDI cores into well-defined dimers, rather than disordered aggregates or micelles. The dimeric building units are rigid yet highly dynamic due to the intrinsic flexibility of the linkers, yielding superlattices with programmable PDI packing geometries and adaptiveness upon structural modifications. For most PDI crystals, PDI units stack continuously in one dimension to maximize interactions, which tend to hinder charge separation. Here, DNA not only encodes sequence-specific interactions but also sterically and electrostatically isolates PDI dimers as discrete photonic units into solid-state optically active materials. The structural tunability of the system can be readily adjusted by varying the PDI core or the linker length between the PDI core and the DNA shell. Notably, these superlattices exhibit photoinduced symmetry-breaking charge transfer distinct from that of monomers or micellar aggregates.
Cuizheng Zhang, Yi Xie, G. Mantel et al.· Journal of the American Chem...· 0 citations
DNA-mediated colloidal crystal engineering offers a powerful route for constructing three-dimensional nanoparticle superlattices with programmable structures and properties. However, achieving room-temperature fabrication of DNA-bonded colloidal crystals with long-range order remains challenging because nanoparticle assemblies are often kinetically trapped in metastable states. Here, we present a simplified enthalpy-regulation strategy based on a toehold-exchange mechanism to control interactions between DNA-functionalized gold nanoparticles. By tuning the relative lengths of the forward and reverse toeholds and the concentration of a DNA trigger, nanoparticle aggregation kinetics are precisely regulated, enabling a symmetric binary system to circumvent kinetic trapping and assemble into high-quality BCC superlattices. We further extend this approach to an asymmetric binary system, where selective control of linker valence directs the formation of distinct CsCl and AlB2 superlattices. Owing to its simplicity and adaptability, this strategy provides a versatile platform for integrating diverse DNA circuits with colloidal crystal assembly and engineering programmable phase behaviors.
Yun Wang, Wen-Qiang Hua, D. Ni et al.· Nano letters (Print)· 0 citations
DNA nanostructures can be tailored to perform a wide variety of functions, with continued interest in biological applications. Some aspects of DNA nanostructure assembly can hinder the ability of nanostructures to be useful in physiological environments. Typical assembly methods employ magnesium ions to stabilize the structure, which leave the structure susceptible to damage by nucleases in body fluids. Further, DNA nanostructure assembly typically involves a thermal annealing protocol in which DNA strands are heated in a specific buffer to a high temperature and cooled slowly at specific rates, preventing convenient encapsulation of temperature-sensitive guest molecules. In this work, we demonstrate the assembly of a wide variety of DNA nanostructures and 3D crystals in a hydrated ionic liquid (choline dihydrogen phosphate, CDHP) instead of magnesium at constant moderate temperatures, thus avoiding thermal annealing. CDHP-assembled structures show enhanced biostability against a variety of nucleases. Molecular dynamics simulations show that choline ions stabilize DNA nanostructures by a direct and close-range interaction in contrast to the predominantly water-mediated interactions of Mg2+, leading to enhanced nuclease resistance in CDHP-containing environments. CDHP-assembled structures do not affect the viability of HepG2 cells and show higher cell internalization. Overall, this work develops a potential method to construct more biostable DNA nanostructures and 3D crystals in a simple one-tube process. Assembly of DNA nanostructures under isothermal conditions is desirable for scaffolding biomolecules and to reduce the need for thermal annealing instruments, allowing nanostructure preparation in low-resource settings.
Double‐stranded DNA molecules are sharply bent into arcs with radii on the order of 10 nanometers in the formation of nucleosomes in biology and when they are looped into minicircles for nanoscale applications. In this Personal Account, we describe our computational efforts over the past several years to understand the structure and dynamics of sharply bent DNA using molecular dynamics simulations. First, using coarse‐grained models of DNA and cationic nanoparticles, we discuss how a small difference in sequence‐dependent DNA flexibility, on the order of 10 nm in persistence length, substantially influences the structure and thermodynamics of DNA–nanoparticle complex formation. Potential of mean force calculations quantify the thermodynamic preference for nanoparticle binding to more flexible DNA, with the free energy difference arising primarily from the sequence‐dependent elastic energy of DNA bending. We then turn to all‐atom simulations of DNA minicircles with approximately 90 base pairs. Sequence‐dependent coupling between DNA bending and its helical twist is identified for specific dinucleotide steps, and the internal dynamics of poloidal rotation and in‐plane circular vibration are characterized on time scales of tens and several nanoseconds, respectively. Finally, we present our recent investigations of mechanically interlocked DNA nanostructures: rotaxanes, in which a DNA minicircle is threaded onto a linear DNA axle, and catenanes, composed of two mutually interlocked DNA minicircles. The effects of torsional stress‐induced shape distortion on the structure and dynamics of these topologically constrained architectures are discussed. Together, these studies illustrate how the interplay of DNA sequence, flexibility, and topology governs the behavior of sharply bent DNA, providing molecular‐level insights for the design of DNA‐based nanoscale devices.
Yeonho Song, Jun Soo Kim· Bulletin of the Korean Chemi...· 0 citations
Colloidal crystals with the cubic diamond structure are attractive templates for three-dimensional photonic band-gap materials, but their self-assembly is hindered by the need for tetrahedral coordination and staggered next-nearest-neighbor bonds, which together impose substantial kinetic barriers in previously realized DNA-mediated systems. Here we demonstrate an entropically guided, non-site-specific route to colloidal diamond that uses the depletion interaction to assemble tetrahedrally lobed patchy particles (TLPPs). The nonconvex TLPP shape encodes the staggered geometry and permits multiple sequential contacts between neighbors, so excluded-volume overlap increases progressively as particles approach the fully interlocked configuration. Using polymer micelles (Pluronic F127) as depletants, as well as silica and titania nanoparticles and polyethylene oxide, we obtain cubic-diamond crystals that form at lower particle concentrations and on timescales about an order of magnitude faster than TLPPs linked through DNA-coated patches. Optical microscopy of fluorescently labeled, refractive-index-matched particles confirms three-dimensional diamond order and predominantly ABC stacking of the {111} planes through analysis of bond networks, radial distribution functions, and a threefold bond-orientational order parameter. Monte Carlo excluded-volume calculations and umbrella sampling show that increasing depletion strength reshapes the potential of mean force into a broad, funnel-like landscape toward the fully interlocked subkissing state, substantially reducing the rotational entropic barrier to binding. Finally, we show that depletion-assembled structures can be permanently fixed by hybridization of palindromic DNA linkers followed by ultraviolet light (UV)-induced thymine photodimerization, enabling washing, drying, and downstream conversion to inverse photonic lattices.
Min Jae Kim, Xinhang Shen, Min Kyung Lee et al.· Proceedings of the National...· 0 citations
The influence of hydrophobic microenvironments on the self-assembly and structural dynamics of nucleotides remains fundamentally elusive at the molecular level. Here, we establish a robust biomimetic platform utilizing a Fe(III)-nucleoside monophosphate-TPA ternary complex, where the bulky TPA ligand serves as a tailored “hydrophobic umbrella”. High-resolution crystallographic investigations reveal that this localized confinement drives 5′-coordinated nucleotides to spontaneously assemble into discrete biological architectures, such as A-motifs and i-motifs. Translating these solid-state findings to aqueous solution, circular dichroism (CD) spectroscopy provides experimental validation of the supramolecular mechanism. Solvent-dependent titrations reveal a sharp, nonlinear sigmoidal phase transition, explicitly demonstrating that the TPA scaffold actively overrides the chaotic, isodesmic π–π stacking characteristic of free nucleotides. Instead, the rigid chiral locking of the assembly is cooperatively driven by the massive thermodynamic compressive forces of hydrophobic exclusion. Comprehensive computational modeling, including DFT, NCI, and Hirshfeld surface analyses, unequivocally maps and quantifies this driving force, isolating the explicit energetic stabilization provided by the dispersive hydrophobic shield. Furthermore, we resolve the paradoxical role of solvent within these confined cavities: while bulk water is aggressively repelled, a specifically localized primary hydration shell is strictly preserved. This inner hydration layer acts as a master thermodynamic determinant, mechanically locking the precise biomimetic sugar ring puckering (C3′-endo/C2′-exo) requisite for assembly. Collectively, these integrated structural, spectroscopic, and thermodynamic insights illuminate the physicochemical forces governing nucleic acid organization in restricted spaces, offering a definitive supramolecular model for biological molecular recognition.
A. Pal, M. Nethaji· Crystal Growth & Design· 0 citations
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