Three-dimensional protein crystals are ordered, porous macroscopic materials with potential applications in catalysis, biosensing, and biomedicine. However, most protein crystals are obtained by empirical screening, providing limited control over the lattice architecture, pore geometry or component composition that determine material function. Here, we present a modular strategy for the programmable design of highly porous, framework-like protein crystals using predefined protein-protein interactions. This strategy yielded over 30 distinct protein crystals, including single-component and multicomponent P213 and I213 lattices that grow to over 100 µm in size. Small-angle X-ray scattering and electron microscopy showed close agreement between experimental lattices and computational models. RFdiffusion-guided design generated isomorphous variants with matched lattice parameters, enabling coherent protein crystal alloys, epitaxial core–shell growth and reversible shell assembly. The designed crystals exhibit tunable mesoporous architectures, with limiting apertures of 2–18 nm, and support genetically encoded incorporation of fluorescent protein guests. These results establish a general route to programmable lattice engineering of protein crystals and position them as genetically encoded, compositionally tunable mesoporous materials.
Organic semiconductor crystals with long-range order and designable properties are pivotal in optoelectronic devices. Organic crystals bonded by weak intermolecular interactions usually follow non-classical crystallization trajectories, yielding polymorphs with distinctive properties but extremely difficult to control. We present a method for deterministic control of polymorphs, yielding organic microcrystal arrays with distinctive crystal structures and emission spectra. To elucidate the mechanisms of molecular self-assembly, we track the real-time dynamics of molecular nucleation, Ostwald’s ripening, and polymorph formation. Based on this method, we extended our regulation strategy to multiple molecules, achieving programmable polymorphic formation with broadly tunable emission spectra (450–705 nm) and anisotropic polarized emission. On a single substrate, we integrated multidimensional polymorphic information including position, wavelength, intensity, and polarization, constructing a high-density optical information storage platform with an information density of 215 bits/cm2, thereby opening potential technological pathways for future optical information storage technologies.
Modulation and control of the crystalline morphology of porous materials are important for their functionality yet remain underdeveloped. In this study, we report the first example of a porous hydrogen-bonded organic framework (HOF) with helical crystalline morphology. The helical HOF was prepared using pyrene-based tetracarboxylic acid. The formation of helical-shaped and needle-shaped crystals of the HOFs can be controlled by the solvent evaporation rate and temperature during heating. X-ray diffraction analysis indicates that both crystals have the same layered porous structure. Based on these data and theoretical calculations, we propose the hypothesis that certain structural defects are locally generated, which induces nonuniform crystal growth and consequently results in the formation of the helical crystals. The obtained HOFs exhibit thermal stability and permanent porosity with Brunauer-Emmett-Teller (BET) surface area up to 1602 m2 g-1. Interestingly, the helical HOFs exhibited dynamic expansion and contraction through the desorption and adsorption of a guest solvent. Moreover, doping with a second component in the helical HOF enables the modulation of fluorescence properties and crystalline morphology into a double helix. These results highlight the potential of a new category of organic materials: helical porous crystals and morphologically functional organic materials.
Yuzuki Murata, Taito Hashimoto, R. Oketani et al.· Angewandte Chemie· 0 citations
Proteins are increasingly used to guide the crystallization of metal-organic frameworks (MOFs), yielding protein@MOFs (p@MOFs) that encapsulate fragile biomacromolecules within stable crystalline hosts. These biohybrid materials offer tunable porosity and spatial organization that are difficult to achieve with conventional synthesis. Despite their growing importance, the mechanisms by which proteins influence MOF nucleation, crystal growth, and defect formation remain poorly understood. Here, we use a distributed electron microscopy approach to follow the full crystallization pathway of ferritin@ZIF-8 (Fn@ZIF-8). The method combines cryogenic transmission electron microscopy (cryo-TEM), cryogenic electron tomography (cryo-ET), and liquid-phase TEM (LP-TEM) to capture structural transitions over time. Using the ferritin iron oxide core as an intrinsic nanoscale tracer, we visualize the transformation of protein-rich amorphous precursors into crystalline particles that ripen, aggregate, and develop large, surface-accessible cavities. These cavities emerge only during later stages of growth, where localized dissolution and recrystallization restructure the framework. Concurrently, proteins become enriched near the crystal periphery and depleted from cavity-rich regions. Our results suggest that protein organization and dissolution-driven restructuring both contribute to defect formation. This work provides a mechanistic framework for understanding how hierarchical porosity develops in p@MOFs and establishes distributed electron microscopy as an approach for investigating biohybrid crystallization pathways.
Rakia Dhaoui, Justin T. Mulvey, Elmira Baghdadi et al.· Small· 0 citations
Biomolecules are nature's catalysts and recognition elements, yet their practical use is limited by instability and lack of reusability. Crystalline porous organic frameworks (POFs) have emerged as protective hosts, but the field is now shifting from passive encapsulation toward engineering multi-component synergy. This review introduces a new paradigm: moving beyond single-biomolecule immobilization to construct hierarchical, cooperative systems within POFs. The structural regularity, tunable porosity, and versatile functionality of POFs enable the spatial and functional organization of multiple enzymes, nucleic acids, proteins, small bioactive molecules, and even heterogeneous functional components-forming multi-enzyme cascades, nucleic acid-protein assemblies, protein-protein synergistic systems, and heterogeneous integrations with metal nanoparticles, polymers, inorganic components, biological membranes, and living cells-to create artificial organelles and molecular factories that mimic nature's compartmentalization. These synergistic systems enable efficient cascade catalysis, enhanced stability, and emergent functionalities unattainable by single components. We survey their applications in industrial biocatalysis, environmental remediation, and healthcare, while also critically discussing current challenges and future directions. By establishing multi-component synergy as a new design principle, this review provides a roadmap for the next generation of POF-based biohybrids toward sustainable biotechnologies.
Jiaxin Cui, Xin Liu, Jing-Ting He et al.· Chemical Society Reviews· 0 citations
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.
Zhenyu Han, C. Mirkin· Science Advances· 0 citations
Peptide self-assembly and liquid-liquid phase separation (LLPS), often mediated by intrinsically disordered regions (IDRs), are natural mechanisms that translate protein molecular features into complex nano- and mesoscale architectures. Although the thermodynamics and kinetics of these processes are well understood, synthetic materials integrating both functionalities remain rare. Inspired by the conserved IDR-assembly domain (AD) architecture of amyloidogenic proteins, we hypothesized that modular recombinant constructs combining LLPS-capable IDRs with β-sheet-forming ADs could generate materials with tunable structural properties. To test this, we engineered a library of elastin-like polypeptides (ELPs) fused to amphiphilic anionic or cationic amyloidogenic peptides, enabling systematic investigation of how sequence parameters─including ELP length, AD charge, and hydrophilicity─and environmental conditions, including temperature, pH, and salt concentration, influence material behavior. Our results reveal links between molecular design and emergent multiscale structures, including micelles and vesicles embedded within coacervates. This work provides a framework for designing hybrid proteins coupling LLPS and self-assembly.
Yulia Shmidov, Li-Xin Fan, Max R. Ney et al.· Biomacromolecules· 0 citations
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