Shunzhi Wang

• Northwestern University

We describe a modular bond-centric approach to protein nanomaterial design inspired by the rich diversity of chemical structures that can be generated from the small number of atomic valencies and bonding interactions. We design protein building blocks with regular coordination geometries and bonding interactions that enable the assembly of a wide...

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by endogenous ligands. Therapeutic approaches such as lysosome-targeting chimaeras1,2 (LYTACs) and cytokine receptor-targeting chimeras³ (KineTACs) have used this to target specific proteins for degradation by fusing modified native ligands to target binding proteins....

Natural photosystems couple light harvesting to charge separation using a ‘special pair’ of chlorophyll molecules that accepts excitation energy from the antenna and initiates an electron-transfer cascade. To investigate the photophysics of special pairs independently of the complexities of native photosynthetic proteins, and as a first step toward...

In principle, designing and synthesizing almost any class of colloidal crystal is possible. Nonetheless, the deliberate and rational formation of colloidal quasicrystals has been difficult to achieve. Here we describe the assembly of colloidal quasicrystals by exploiting the geometry of nanoscale decahedra and the programmable bonding characteristi...

Protein crystallization plays a central role in structural biology. Despite this, the process of crystallization remains poorly understood and highly empirical, with crystal contacts, lattice packing arrangements and space group preferences being largely unpredictable. Programming protein crystallization through precisely engineered side-chain–side...

Endocytosis and lysosomal trafficking of cell surface receptors can be triggered by interaction with endogenous ligands. Therapeutic approaches such as LYTAC1,2 and KineTAC3, have taken advantage of this to target specific proteins for degradation by fusing modified native ligands to target binding proteins. While powerful, these approaches can be...

As a result of evolutionary selection, the subunits of naturally occurring protein assemblies often fit together with substantial shape complementarity to generate architectures optimal for function in a manner not achievable by current design approaches. We describe a "top-down" reinforcement learning-based design approach that solves this problem...

Natural photosystems couple light harvesting to charge separation using a “special pair” of chlorophyll molecules that accepts excitation energy from the antenna and initiates an electron-transfer cascade. To investigate the photophysics of special pairs independent of complexities of native photosynthetic proteins, and as a first step towards synt...

Protein crystallization plays a central role in structural biology, with broad impact in pharmaceutical formulation, drug delivery, biosensing, and biocatalysis. Despite this importance, the process of protein crystallization remains poorly understood and highly empirical, with largely unpredictable crystal contacts, lattice packing arrangements, a...

Despite remarkable advances in the assembly of highly structured coordination polymers and metal-organic frameworks, the rational design of such materials using more conformationally flexible organic ligands such as peptides remains challenging. In an effort to make the design of such materials fully programmable, we first developed a computational...

The multisubunit protein assemblies that play critical roles in biology are the result of evolutionary selection for function of the entire assembly, and hence the subunits in structures such as icosahedral viral capsids often fit together with remarkable shape complementarity 1,2 . In contrast, the large multisubunit assemblies that have been crea...

Nature has evolved a vast repertoire of structures and functions based on an ordered, orchestrated, protein building-blocks assembly. For decades these sophisticated materials have been studied, mimicked, and repurposed, yet recently, computational protein engineering methods provided an alternative route: creating protein materials de-novo, surpas...

Colloidal crystal engineering of complex, low-symmetry architectures is challenging when isotropic building blocks are assembled. Here we describe an approach to generating such structures based upon programmable atom equivalents (nanoparticles functionalized with many DNA strands) and mobile electron equivalents (small particles functionalized wit...

Oligonucleotide-functionalized nanoparticles (NPs), also known as "programmable atom equivalents" (PAEs), have emerged as a class of versatile building blocks for generating colloidal crystals with tailorable structures and properties. Recent studies have shown that, at small size and low DNA grafting density, PAEs can also behave as "electron equi...

Microscopy-Based Approaches to Characterizing Analogs of Classical Electrons in Colloidal Crystals Engineered with DNA - Jingshan Du, Shunzhi Wang, Vinayak Dravid, Chad Mirkin

Colloidal crystal engineering with nucleic acid-modified nanoparticles is a powerful way for preparing 3D superlattices, which may be useful in many areas, including catalysis, sensing, and photonics. To date, the building blocks studied have been primarily based upon metals, metal oxides, chalcogenide semiconductors, and proteins. Here, we show th...

Colloidal crystal engineering with DNA has emerged as a powerful tool for precisely controlling the arrangement of nanoscale building blocks in three-dimensional superlattices, where nanoparticles densely modified with DNA can be viewed as "programmable atom equivalents" (PAEs). Although a wide variety of complementary DNA-modified nanoparticles, d...

Mobile particles in colloidal crystals The crystallization of nanoparticles can be controlled by functionalizing them with DNA strands that direct assembly through hybridization. The design rules for interactions between pairs of particles resemble those for ionic compounds. Inspired by molecular dynamics simulations, Girard et al. show that larger...

Phases of multielement nanoparticles Thermodynamically stable metal nanoparticles composed of multiple elements could, in principle, exhibit several different phases that form multiple interfaces. Chen et al. explored the structure and composition of palladium-tin alloy nanoparticles formed with up to five other elements after high-temperature anne...

Due to their large size, charged surfaces, and environmental sensitivity, proteins do not naturally cross cell-membranes in intact form and, therefore, are difficult to deliver for both diagnostic and therapeutic purposes. Based upon the observation that clustered oligonucleotides can naturally engage scavenger receptors that facilitate cellular tr...

Although macroscopic metal–organic framework (MOF) single crystals have been routinely synthesized, undesired impurity phases are sometimes obtained in MOF nanoparticle (NP) syntheses, where purification remains challenging. Herein we report an electrostatic adsorption strategy to separate mixed phases of MOF NPs on the basis of their metal cluster...

Due to their well‐defined 3D architectures, permanent porosity, and diverse chemical functionalities, metal–organic framework nanoparticles (MOF NPs) are an emerging class of modular nanomaterials. Herein, recent developments in the synthesis and postsynthetic surface functionalization of MOF NPs that strengthen the fundamental understanding of how...

Stimuli-responsive nanomaterials with reconfigurable structures and properties have garnered significant interest in the fields of optics, electronics, magnetics, and therapeutics. DNA is a powerful and versatile building material that provides programmable structural and dynamic properties, and indeed, sequence-dependent changes in DNA have alread...

Metal-organic frameworks (MOFs) are a class of modular, crystalline, and porous materials that hold promise for storage and transport of chemical cargoes. Though MOFs have been studied in bulk forms, ways of deliberately manipulating the external surface functionality of MOF nanoparticles are less developed. A generalizable approach to modify their...

Nanoscale UiO-66 Zr6(OH)4O4(C8O4H4)6 has been synthesized with a series of carboxylic acid modulators, R-COOH (where R = H, CH3, CF3, and CHCl2). The phase purity and size of each MOF was confirmed by powder X-ray diffraction, BET surface area analysis, and scanning transmission electron microscopy (STEM). Size control of UiO-66 crystals from 20 nm...

Multimetal nanoparticle synthesis Multicomponent nanoparticles can be difficult to synthesize. Rather than mixing in one type of particle, the compounds often separate and form distinct particles. Using dip-pen lithography, Chen et al. show how adding reactants to very small volumes forces the reactants to form single particles containing various c...

A method for modifying the external surfaces of a series of nanoscale metal-organic frameworks (MOFs) with 1,2-dioleoyl-sn-glycero-3-phosphate (DOPA) is presented. A series of zirconium-based nanoMOFs of the same topology (UiO-66, UiO-67, and BUT-30) were synthesized, isolated as aggregates, and then conjugated with DOPA to create stably dispersed...

The concept of using cantilever-free scanning probe arrays as structures that can modulate nanoscale ink flow and composition with light is introduced and evaluated. By utilizing polymer pen arrays with an opaque gold layer surrounding the base of the transparent polymer pyramids, we show that inks with photopolymerizable or isomerizable constituen...

A 6,8-connected 3-dimensional metal–organic framework (2) of the tph topology was constructed from a new aromatic-rich, tetraphenylmethane-derived octa-carboxylate bridging ligand and trizinc cluster secondary building units (SBUs), and exhibited exceptionally high hydrogen (58 mg g−1 and 39 g L−1 at 52 bar and 77 K) and methane (276 mg g−1 and 189...

Nanoscale coordination polymers containing exceptionally high loadings of bisphosphonates were coated with single lipid bilayers to control the drug release kinetics and functionalized with a targeting ligand to endow cell-targeting capability, leading to much enhanced cytotoxicity against human lung and pancreatic cancer cells.