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1. Dynamics in supramolecular nanomaterials

   https://doi.org/10.1039/d1sm00047k  

   Cho, Yukio; Christoff-Tempesta, Ty; Kaser, Samuel J.; Ortony, Julia H. (June 2021, Soft Matter)

   Self-assembly of amphiphilic small molecules in water leads to nanostructures with customizable structure–property relationships arising from their tunable chemistries. Characterization of these assemblies is generally limited to their static structures – e.g. their geometries and dimensions – but the implementation of tools that provide a deeper understanding of molecular motions has recently emerged. Here, we summarize recent reports showcasing dynamics characterization tools and their application to small molecule assemblies, and we go on to highlight supramolecular systems whose properties are substantially affected by their conformational, exchange, and water dynamics. This review illustrates the importance of considering dynamics in rational amphiphile design. 

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2. Hybrid Bonding Bottlebrush Polymers Grafted from a Supramolecular Polymer Backbone

   https://doi.org/10.1021/jacs.4c03320  

   Clemons, Tristan D; Egner, Simon A; Grzybek, Joseph; Roan, Joshua J; Sai, Hiroaki; Yang, Yang; Syrgiannis, Zois; Sun, Hao; Palmer, Liam C; Gianneschi, Nathan C; et al (June 2024, Journal of the American Chemical Society)

   Bottlebrush polymers, macromolecules consisting of dense polymer side chains grafted from a central polymer backbone, have unique properties resulting from this well-defined molecular architecture. With the advent of controlled radical polymerization techniques, access to these architectures has become more readily available. However, synthetic challenges remain, including the need for intermediate purification, the use of toxic solvents, and challenges with achieving long bottlebrush architectures due to backbone entanglements. Herein, we report hybrid bonding bottlebrush polymers (systems integrating covalent and noncovalent bonding of structural units) consisting of poly(sodium 4-styrenesulfonate) (p(NaSS)) brushes grafted from a peptide amphiphile (PA) supramolecular polymer backbone. This was achieved using photoinitiated electron/energy transfer-reversible addition–fragmentation chain transfer (PET-RAFT) polymerization in water. The structure of the hybrid bonding bottlebrush architecture was characterized using cryogenic transmission electron microscopy, and its properties were probed using rheological measurements. We observed that hybrid bonding bottlebrush polymers were able to organize into block architectures containing domains with high brush grafting density and others with no observable brushes. This finding is possibly a result of dynamic behavior unique to supramolecular polymer backbones, enabling molecular exchange or translational diffusion of monomers along the length of the assemblies. The hybrid bottlebrush polymers exhibited higher solution viscosity at moderate shear, protected supramolecular polymer backbones from disassembly at high shear, and supported self-healing capabilities, depending on grafting densities. Our results demonstrate an opportunity for novel properties in easily synthesized bottlebrush polymer architectures built with supramolecular polymers that might be useful in biomedical applications or for aqueous lubrication. 

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3. Electromechanical switching in DNA–CNT supramolecular structures

   https://doi.org/10.1063/5.0272693  

   Alolaiyan, Olaiyan; De, Arpan; Anantram, M P (July 2025, Applied Physics Letters)

   The characteristics of the interface between DNA and metallic carbon nanotube (CNT) in supramolecular assemblies are important to understand for electronic and sensing applications. We study the mechanical stability and electronic properties of these interfaces with amino and ester linkers using computational experiments. Our study demonstrates that both linkers significantly enhance the mechanical stability of DNA–CNT systems, with the DNA adopting a stable and lower energy perpendicular orientation relative to the CNT as opposed to a conventional parallel arrangement. This lower energy configuration is driven by nonbonded interactions between the DNA base and the CNT surface. Our calculations also reveal that interface resistance is primarily governed by DNA–CNT interactions with negligible contribution from the linkers. In the case of the amino linker, we predict a 100-fold transmission ratio between parallel and perpendicular configurations of DNA relative to CNT. This observation can be used to build an electromechanical switch with fast switching times (30 ns). The ester linker, on the contrary, enables a better electronic coupling between the DNA and CNT even when strained. 

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4. Conformationally Locked Peptide–DNA Nanostructures for CRISPR‐Amplified Activity‐Based Sensing

   https://doi.org/10.1002/anie.202500649  

   Snider, Dylan M; Coffin, Mackenzie L; Armijo, Brian J; Khetan, Ryan; Duchow, Mark W; Capasso, Anna; Samanta, Devleena (June 2025, Angewandte Chemie International Edition)

   Abstract We introduce a new class of chemical probes for activity‐based sensing of proteases, termed cleavable, locked initiator probes (CLIPs). CLIPs contain a protease‐cleavable peptide linked between two programmable DNA strands—an “initiator” DNA and a shorter “blocking” DNA. These DNA sequences are designed to hybridize, creating a “locked” hairpin‐like structure. Upon proteolytic cleavage, the initiator strand is released, triggering the activation of CRISPR‐Cas12a enzymes and producing an amplified fluorescence response. CLIPs generate more than 20‐fold turn‐on signals at room temperature (25 °C), significantly outperforming commercial probes by yielding ∼40‐fold lower limits of detection (LOD) at 100‐fold lower concentrations. Their versatility enables the detection of various disease‐relevant proteases—including the SARS‐CoV‐2 main protease, caspase‐3, matrix metalloproteinase‐7, and cathepsin B—simply by altering the peptide sequence. Importantly, CLIPs detect cathepsin B in four different colorectal cancer cell lines, highlighting their clinical potential. Taken together, the sensitivity (LOD: ∼88 pM), selectivity, and rapid assay time (down to 35 min), combined with the ability to operate in complex biological media with minimal sample preparation, position CLIPs as powerful chemical tools for activity‐based sensing of functional enzymes. 

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5. Predicting rare DNA conformations via dynamical graphical models: a case study of the B→A transition

   https://doi.org/10.1093/nar/gkaf601  

   De Silva, Namindu; Perez, Alberto (July 2025, Nucleic Acids Research)

   Abstract DNA exhibits local conformational preferences that affect its ability to adopt biologically relevant conformations, such as those required for binding proteins. Traditional methods, like Markov state models and molecular dynamics (MD) simulations, have advanced our understanding but often struggle to capture these rare conformational states due to high computational demands. Here, we introduce a novel AI framework based on dynamical graphical models (DGMs), a generative machine learning approach trained on equilibrium MD data, to predict DNA conformational transitions that are never seen in the MD ensembles. By leveraging local DNA interactions, DGMs generate a comprehensive transition matrix that captures both thermodynamic and kinetic properties of unsampled states, enabling accurate predictions of rare global conformations without the need for extensive sampling. Applying this model to the B→A transition, we demonstrate that DGMs can efficiently predict sequence-dependent A-DNA preferences, achieving results that align closely with replica exchange umbrella sampling simulations. DGMs provide new insights into DNA sequence–structure relationships, paving the way for applications in DNA sequence design and optimization. 

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