Search for: All records

Peptide coassembly offers novel opportunities for designing advanced nanomaterials. This study used coarse-grained molecular dynamics simulations to examine the coassembly of charge-complementary peptides, assessing various ratios and the role of charge and hydrophobicity in their aggregation. We discovered that peptide length, charge, and hydrophobicity significantly influence coassembly behavior, with more hydrophobic peptides exhibiting greater aggregation despite electrostatic repulsion. Beyond the coassembly of two peptides, we also observed that the coassembly of more than two peptides will likely lead to new assembly structures and properties. Our findings underscore the importance of peptide composition and length in tuning the coassembly and the resulting properties, thus facilitating the design of complex peptide nanoparticles for biomedical and biotechnological applications. 

Wireframe DNA nanocages, an important type of DNA nanomaterials, exhibit exceptional programmability for chemical modifications, along with tunable size and shape. Nevertheless, the impact of their conformational fluctuations on cage design has not been thoroughly explored, despite speculation regarding its influence on biomedical applications. This study marks the first systematic examination of the conformational dynamics of prismatic DNA nanocages through molecular modeling and simulation. By comparing four different DNA nanocage topologies, we uncover design parameter combinations and conditions that facilitate access to varying conformational states. We observe the expansion and contraction of these cages across various topologies, hybridization states, and ionic environments (Mg2+/Na+), with their volumes varying from 15% to 150% of the ideal cage volumes. Our results indicate that the dynamics of DNA cages is influenced by the concentrations of Mg2+ and Na+ ions. Additionally, the flexibility of specific DNA strands can be manipulated, thereby altering the cage volume, through the selective hybridization of the cage edges. Ultimately, the conformational dynamics of DNA nanocages are captured in atomic detail. This study offers valuable modeling tools and methodologies to assist future DNA nanocage design endeavors. 

Geometric isomerism in mechanically interlocked systems — which arises when the axle of a mechanically interlocked molecule is oriented, and the macrocyclic component is facially dissymmetric — can provide enhanced functionality for directional transport and polymerization catalysis. We now introduce a kinetically controlled strategy to control geometric isomerism in [2]rotaxanes. Our synthesis provides the major geometric isomer with high selectivity, broadening synthetic access to such interlocked structures. Starting from a readily accessible [2]rotaxane with a symmetrical axle, one of the two stoppers is activated selectively for stopper exchange by the substituents on the ring component. High selectivities are achieved in these reactions, based on coupling the selective formation reactions leading to the major products with inversely selective depletion reactions for the minor products. Specifically, in our reaction system, the desired (major) product forms faster in the first step, while the undesired (minor) product subsequently reacts away faster in the second step. Quantitative 1H NMR data, fit to a detailed kinetic model, demonstrates that this effect (which is conceptually closely related to minor enantiomer recycling and related processes) can significantly improve the intrinsic selectivity of the reactions. Our results serve as proof of principle for how multiple selective reaction steps can work together to enhance the stereoselectivity of synthetic processes forming complex mechanically interlocked molecules. 

Abstract Modern molecular detection assays such as enzyme‐linked immunosorbent assays (ELISAs) offer excellent sensitivity and specificity, but typically require multiple reagents and extensive sample preparation, limiting their usefulness as rapid diagnostics. A generalizable biosensor platform is introduced that enables single‐step, sample preparation‐free detection of protein analytes with high sensitivity in complex samples. The NanoFluor system employs Janelia Fluor dyes coupled to a nanobody via HaloTag conjugation with a flexible glycine‐serine linker, where the dye undergoes a switch from a non‐fluorescent to a fluorescent state when the coupled nanobody binds to its target. It is demonstrated that the NanoFluor design achieves detection limits as low as picomolar concentrations across diverse protein targets. Molecular dynamics simulations, coupled with quantum mechanics/molecular mechanics computational models, reveal the mechanistic basis for the fluorescence change, and demonstrate the feasibility of multiplexed detection in complex samples including undiluted serum. This versatile, simple biosensor design can prove valuable for point‐of‐care diagnostics and other molecular detection applications. 

Abstract Two‐dimensional (2D) assemblies of water‐soluble block copolymers have been limited by a dearth of systematic studies that relate polymer structure to pathway mechanism and supramolecular morphology. Here, we employ sequence‐defined triblock DNA amphiphiles for the supramolecular polymerization of free‐standing DNA nanosheets in water. Our systematic modulation of amphiphile sequence shows the alkyl chain core forming a cell membrane‐like structure and the distal π‐stacking chromophore block folding back to interact with the hydrophilic DNA block on the nanosheet surface. This interaction is crucial to sheet formation, marked by a chiral “signature”, and sensitive to DNA sequence, where nanosheets form with a mixed sequence, but not with a homogeneous poly(thymine) sequence. This work opens the possibility of forming well‐ordered, bilayer‐like assemblies using a single DNA amphiphile for applications in cell sensing, nucleic acid therapeutic delivery and enzyme arrays.