Molecular Systems Design & Engineering最新文献

There exist numerous opportunities to design stimuli-responsive bilayer hydrogels for enhanced actuation using simple and robust techniques. Specifically, digital light processing (DLP) 3D printing offers a robust technique for multi-layered hydrogel fabrication. However, nanocomposite hydrogels utilizing this technique have not yet been widely realized. Nanoclay incorporation has been shown to improve the actuation of poly(N-isopropyl acrylamide) (pNIPAAm) hydrogels; however, opportunities remain to study the relationship between clay morphology and thermal response, particularly in a 3D-printed bilayer system. In this work, we utilized an ethanol-water cosolvent, hydrogel precursor solution to incorporate montmorillonite (MMT) clay into 3D-printed pNIPAAm hydrogels. By varying the MMT loading, we demonstrated that a low loading of MMT (0.5 wt% relative to the mass of NIPAAm monomer) induced the greatest enhancement of the initial rate and final magnitude of actuation in the studied hydrogels. We utilized poly(2-hydroxyethyl acrylate) (pHEA) as a passive layer to form bilayers by sequentially printing pHEA before the pNIPAAm/MMT hydrogels, and used those hydrogels to demonstrate the accelerated actuation of 3D-printed pNIPAAm/MMT-pHEA bilayers compared to clay-free, pNIPAAm-pHEA bilayers. Through comparison to a mathematical framework and fabrication of an all-pNIPAAm bilayer, we suggested that the model has limitations for the prediction of bilayer curvature in these systems due to the inability of certain hydrogels to overcome the inertia of the passive layer. Overall, this work showcases the utility of MMT as a handle for tunability in 3D-printed pNIPAAm bilayer hydrogels.

Taking inspiration from natural systems, such as spider silk and mollusk nacre, that employ hierarchical assembly to attain robust material performance, we leveraged matrix-filler interactions within reinforced polymer-peptide hybrids to create self-assembled hydrogels with enhanced properties. Specifically, cellulose nanocrystals (CNCs) were incorporated into peptide-polyurea (PPU) hybrid matrices to tailor key hydrogel features through matrix-filler interactions. Herein, we examined the impact of peptide repeat length and CNC loading on hydrogelation, morphology, mechanics, and thermal behavior of PPU/CNC composite hydrogels. The addition of CNCs into PPU hydrogels resulted in increased gel stiffness; however, the extent of reinforcement of the nanocomposite gels upon nanofiller inclusion also was driven by PPU architecture. Temperature-promoted stiffening transitions observed in nanocomposite PPU hydrogels were dictated by peptide segment length. Analysis of the peptide secondary structure confirmed shifts in the conformation of peptidic domains (α-helices or β-sheets) upon CNC loading. Finally, PPU/CNC hydrogels were probed for their injectability characteristics, demonstrating that nanofiller-matrix interactions were shown to aid rapid network reformation (∼10 s) upon cessation of high shear forces. Overall, this research showcases the potential of modulating matrix-filler interactions within PPU/CNC hydrogels through strategic system design, enabling the tuning of functional hydrogel characteristics for diverse applications.

Developments related to large language models (LLMs) have deeply impacted everyday activities and are even more significant in scientific applications. They range from simple chatbots that respond to a prompt to very complex agents that plan, conduct, and analyze experiments. As more models and algorithms continue to be developed at a rapid pace, the complexity involved in building this framework increases. Additionally, editing these algorithms for personalized applications has become increasingly challenging. To this end, we present a modular code template that allows easy implementation of custom Python code functions to enable a multi-agent framework capable of using these functions to perform complex tasks. We used the template to build DynaMate, a complex framework for generating, running, and analyzing molecular simulations. We performed various tests that included the simulation of solvents and metal–organic frameworks, calculation of radial distribution functions, and determination of free energy landscapes. The modularity of these templates allows for easy editing and the addition of custom tools, which enables rapid access to the many tools that can be involved in scientific workflows.

The orientation of integral membrane proteins (IMPs) with respect to the membrane is established during protein synthesis and insertion into the membrane. After synthesis, IMP orientation is thought to be fixed due to the thermodynamic barrier for “flipping” protein loops or helices across the hydrophobic core of the membrane in a process analogous to lipid flip-flop. A notable exception is EmrE, a homodimeric IMP with an N-terminal transmembrane helix that can flip across the membrane until flipping is arrested upon dimerization. Understanding the features of the EmrE sequence that permit this unusual flipping behavior would be valuable for guiding the design of synthetic materials capable of translocating or flipping charged groups across lipid membranes. To elucidate the molecular mechanisms underlying flipping in EmrE and derive bioinspired design rules, we employ atomistic molecular dynamics simulations and enhanced sampling techniques to systematically investigate the flipping of truncated segments of EmrE. Our results demonstrate that a membrane-exposed charged glutamate residue at the center of the N-terminal helix lowers the energetic barrier for flipping (from ∼12.1 kcal mol⁻¹ to ∼5.4 kcal mol⁻¹) by stabilizing water defects and minimizing membrane perturbation. Comparative analysis reveals that the marginal hydrophobicity of this helix, rather than the marginal hydrophilicity of its loop, is the key determinant of flipping propensity. Our results further indicate that interhelical hydrogen bonding upon dimerization inhibits flipping. These findings establish several bioinspired design principles to govern flipping in related materials: (1) marginally hydrophobic helices with membrane-exposed charged groups promote flipping, (2) modulating protonation states of membrane-exposed groups tunes flipping efficiency, and (3) interhelical hydrogen bonding can be leveraged to arrest flipping. These insights provide a foundation for engineering synthetic peptides, engineered proteins, and biomimetic nanomaterials with controlled flipping or translocation behavior for applications in intracellular drug delivery and membrane protein design.

Developing new negative emission technologies (NETs) to capture atmospheric CO₂ is necessary to limit global temperature rise below 1.5 °C by 2050. The technologies, such as direct air capture (DAC), rely on sorption materials to harvest trace amounts of CO₂ from ambient air. Deep eutectic solvents (DESs) and eutectic solvents (ESs), a subset of ionic liquids (ILs), are all promising new CO₂ sorption materials for DAC. However, the experimental design space for different DESs/ESs/ILs is vast, with the exact CO₂ complexation pathways difficult to elucidate; this creates significant limitations in rationally designing new materials with targeted CO₂ sorption energetics. Herein, the CO₂ complexation pathways for a structural library of different DES/ES components are computed using quantum chemical calculations (i.e., density functional theory). For the entire structure library, we report the energies of elementary CO₂ binding and proton transfer reactions as these reactions are fundamental in DAC within DESs and ESs. These elementary reactions are combined to generate CO₂ complexation pathways and calculate their free energies. The different elementary steps and reaction pathways demonstrate the range of CO₂ complexation free energies and the significance between CO₂ binding and proton transfer reactions. We also report the CO₂ complexation free energies with different functional groups around the CO₂ sorption site, supporting the concept of functionalization for tuning CO₂ complexation thermodynamics. Additionally, our findings suggest potential descriptors, such as proton affinity or pK_a, could be useful when identifying candidate species for ESs and predicting/rationalizing product distributions. Our work has implications for experimental synthesis, characterization, and performance evaluation of new DAC sorption materials.

A hybrid mesoscopic simulation approach combining multiple particle collision dynamics (MPCD) with molecular dynamics (MD) is employed to investigate the dynamic behaviors and conformational changes of semi-flexible [2]catenanes with varying ring sizes under steady shear flow conditions. Firstly, our study reveals an irregular linear relationship between the three-dimensional surface area of the rings and the shear rate, as evidenced by changes in the surface area of the semi-flexible [2]catenane. Through schematic observations, we find that the dynamic behaviors of [2]catenanes differ for varying ring sizes. Small rings exhibit tumbling motions, medium rings show slip-tumbling motions, while large rings undergo fold-slipping motions. Medium and large rings show shear thinning conformation changes. Secondly, we analyze the normal and diagonal angles of the two rings, demonstrating that the movements in both the shear direction and the gradient direction are complete but intermittent. Thirdly, we analyze how the relative displacement vector of the center of mass between the two rings in the [2]catenane changes over time. This analysis indication of the relative motion occurring between the two rings. We also find that within certain ranges of shear rate and ring size, the two rings of the [2]catenane twist into “8” shapes, rather than slip-tumbling and fold-slipping motions. These findings provide valuable insights for guiding the transport of catenane polymers in biological systems and for designing catenane polymeric materials for industrial applications.

Intrinsically disordered proteins (IDPs) yield solutions with tunable phase transition behavior and have been widely applied in designing stimuli-responsive materials. Understanding interactions between amino acid residues of the IDP sequence is critical to designing new IDP-based materials with selective phase behavior, assembly, and mechanical properties. The lack of defined structure for this class of proteins complicates accurate prediction of their molecular-scale behavior. In this review, recent progress is presented in the development and application of simulation methods to describe the behavior of IDPs. Results for elastin-like polypeptides (ELPs) and resilin-like polypeptides (RLPs) are highlighted, focusing on studies that compare simulation results with experimental findings.

This study presents a cross-linked bisphenol A propoxylate diglycidyl ether network (BP17) synthesised via a dynamic transesterification reaction. The reaction involves a linear long chain bisphenol A propoxylate diglycidyl ether terminated (BP), high molecular weight cross-linker viz., Pripol 1017, and Zn(OAc)₂ as a catalyst. The thermal dynamics of the BP17 network are investigated using creep recovery tests. BP17 shows appreciable resistance to solvents such as dimethyl sulfoxide (DMSO), even at 160 °C. Thermogravimetric analysis reveals its excellent thermal stability, with an onset degradation temperature of 290 °C. In addition, it could be reprocessed by hot-pressing at 160 °C, retaining its mechanical properties even after the third cycle. Moreover, the cytocompatibility test confirms the biocompatibility of BP17, making it a promising candidate for use in maxillofacial prosthetics. Thus, the thermoset-like properties of BP17, at relatively high temperature, make it very promising for biomedical and other advanced applications.

Salmonellae, which pose a significant global health threat, cause a range of infections, including gastroenteritis and, in severe cases, meningitis, particularly in immunocompromised individuals. The emergence of multi-drug-resistant Salmonella enterica serovar Typhimurium underscores the urgent need for effective vaccine development. In this study, a chimeric vaccine was constructed, targeting UPF0721 transmembrane proteins of serovar Typhimurium strain L-4126, which are critical for its life cycle. Fifteen highly antigenic epitopes, including CTL, HTL, and B-cell epitopes, were recognised and assessed for their ability to elicit T-cell and IFN-γ-mediated immune-responses. Physiochemical analyses confirmed their safety profiles. The vaccine construct integrated these epitopes with linkers (EAAAK, GPGPG, AAY, and KK) and β-defensin adjuvants to enhance immunogenicity, stability, and molecular interactions. Molecular docking demonstrated robust binding affinity, particularly with TLR8, and highlighted the vaccine's structural stability and immunogenic potential. The eigenvalue analysis (9.728895) validated the vaccine's flexibility and favorable biophysical properties. Molecular dynamics simulations validated the energy minimization, molecular stability and flexibility assessments. Immune simulation results indicated strong immune responses, while the physicochemical analysis confirmed solubility and stability during recombinant peptide expression in E. coli. This study also explored mRNA vaccine constructs, emphasizing their potential in combating serovar Typhimurium infections such as meningitis. The vaccine construct showed high potential, demanding further investigation into their immune efficacy against serovar Typhimurium infections through experimental assays and medical trials.

Single-atom catalysts (SACs) have attracted great attention due to their distinct advantages; however, their complicated synthesis procedures have impeded their large-scale application. Additionally, nano-particles or subnano-clusters generated during the synthesis can adversely affect the final performance of the catalysts. The appearance of two-dimensional metal–organic frameworks (2D-MOFs) has provided a new strategy to synthesize SACs. Moreover, highly ordered MOFs have high electrical conductivity and are conducive to electron transfer, which is crucial in improving the electrochemical activity of catalysts. A series of single-atom catalysts TM₃(HATNA)₂ (where TM is one of ten different transition metals) based on 2D-MOFs has been designed using hexazine hetero-trinaphthalene (HATNA) as ligands. The mechanisms and routes of the carbon dioxide reduction reaction (CO₂RR) catalyzed by these materials have been studied using first-principles methods. The results testify that TM₃(HATNA)₂ (TM = Cr, Ru and Rh) may serve as potential catalysts for the CO₂RR with good stability and catalytic activity. The reduction product of Cr₃(HATNA)₂ is methane (CH₄), while that of both Ru₃(HATNA)₂ and Rh₃(HATNA)₂ is methanol (CH₃OH). This work provides a new substrate material for the development of single-atom catalysts with abundant and diverse catalytic products.