Specific Interactions Research Articles

The interplay of specific surface interactions as well as ion and hydration structuring takes on a pivotal role in dictating the intermolecular, intersurface, and colloidal behavior at solid-liquid interfaces. The detailed atomic and molecular structure consequently influences a wide array of surface-mediated functions in technological and biological systems. Ion and hydration structuring at the interface is susceptible to various surface parameters, including surface potential, structural modifications including molecular adsorbents, the charge of specific functional groups, and electrolyte composition. Here, we disclose an electromechanical adhesion switch mechanism and demonstrate, in operation, the impact of molecular surface modification and potential modulation on adhesive and repulsive forces between surfaces. We exemplify these fundamental interactions by measuring the acting intermolecular forces between mica and metal surfaces modified with self-assembled monolayers including mercaptobenzimidazole and cysteamine films, showcasing the potential for tailoring surface interactions via ion adsorption manipulation. Employing an electrochemical surface forces apparatus complemented with molecular dynamics simulation, we present a comprehensive analysis of the specific forces involved in film-mica interactions and the impact of ion ordering under electrochemical modulation on such forces. Our results offer a novel perspective on how hydration and ion adsorption shape solid-solid interactions involving organic thin films and how these interactions provide a flexible route for electromechanical adhesion switches.

Pharmacological inhibition of Trypanosoma cruzi aldo-keto reductase (TcAKR) and its effect on benznidazole resistance.

Cellulosic biomass represents a promising feedstock for biofuel and biochemical production. However, its recalcitrant structure strongly hinders enzymatic degradation. Cellulosomes are large multienzyme complexes, highly efficient at degrading cellulose. A cellulase in a cellulosome has a dockerin domain that binds to a cohesin module on the CipA (cellulosome integrating protein A). In a native cellulosome all cohesins are identical, so that the cellulase types and their positions in a CipA cannot be controlled. Here, we constructed the largest designer CipA known to date. Using innovative techniques, we synthesized a designer CipA gene that encodes nine distinct cohesins and two cellulose-binding modules, which we named DCipA2B9C. Then, we fused nine distinct fungal cellulases separately with nine distinct dockerins for their precise positioning on DCipA2B9C to achieve enzyme proximity-effect. We constructed three yeast hosts to compare their performances. First, an enzyme host (EH) secretes nine dockerin-fused cellulases, including endoglucanases (EgIII-a, EgIII-m, and EgIII-c), exoglucanases (CBHII-j and EXG2-r), β-glucosidases (BGS-f and BGS-l), and cellulase boosters, including a LPMO-t and CDH-b. Second, the scaffoldin host (SH) expresses DCipA2B9C. Third, the cellulosome-9 host expresses DCipA2B9C and nine dockerin-fused cellulases. Native-PAGE and ELISA confirmed specific interactions between dockerins and cohesins. Additionally, native-PAGE, SDS-PAGE, and LC-MS verified the successful assembly of the multienzyme complex. Our performance evaluation showed that coculturing of EH and SH outperformed the cellulosome-9 host. It degraded microcrystalline cellulose efficiently to produce 14.29 g/L bioethanol, which surpassed all previously constructed yeast cellulosomes by fourfold or more. In summary, our study provides an effective approach to biomass degradation.

The interaction between DNA and surfactants plays an important role in exploring gene regulation, drug delivery, and nanotechnology. However, the specific interactions with the cationic surfactant leading to the conformational changes in DNA are mainly unknown. This study examines the structure and dynamics of DNA-CTAB interactions using the photophysical properties of 2-aminopurine (2Ap)-labeled single-stranded (2Ap-ssDNA) and double-stranded (2Ap-dsDNA) DNA. CTAB induces cooperative compaction in 2Ap-ssDNA, characterized by fluorescence quenching, spectral red shift, and the formation of aligned lamellar aggregates observed in SEM images and XRD analysis. In contrast, dsDNA undergoes compaction/condensation, manifested by fluorescence enhancement, increased fluorescence lifetime, and mixed lamellar and hexagonal aggregates in SEM and XRD data, suggesting structural denaturation/collapse and compaction/condensation. Circular dichroism (CD) analysis corroborates these findings, showing complete disruption of the B-form structure in 2Ap-dsDNA and enhanced strand compaction in 2Ap-ssDNA. Computational studies, including molecular docking, molecular dynamics simulations, and MM/PBSA calculations, support the experimental observations, revealing that CTAB monomer and micelles bind to dsDNA and ssDNA, driven by electrostatic and hydrophobic interactions. These findings underscore the distinct structural responses of 2Ap-ssDNA and 2Ap-dsDNA to surfactant binding. Overall, this study provides valuable insights into the molecular mechanisms of DNA-surfactant interactions and offers a framework for designing DNA-based nanostructures and therapeutic carriers, leveraging electrostatic and hydrophobic forces to modulate nucleic acid architecture for targeted applications.

The dynamic spatiotemporal organization of macromolecules is key to the proper function of the cell, allowing the exquisite regulation of diverse processes from gene expression to enzymatic function. The formation of biomolecular condensates via phase separation (PS) acts as a general mechanism for selectively concentrating proteins, nucleic acids and metabolites in membraneless compartments and thus modulating their activity. Recent studies suggest that plants broadly exploit PS to perceive and quickly respond to their environment, altering transcriptional outputs as a function of changing environmental stimuli. Here, we provide examples of how PS properties contribute to modulating plant environmental response with a focus on gene expression at the transcriptional level and discuss the mechanisms of action of phase-separating proteins and the importance of specific protein-protein interactions for nucleation of PS.

A highly sensitive and selective electrochemical immunosensor was developed for the detection of the cancer biomarker alpha-fetoprotein (AFP), a key indicator of cancer. This sensor utilizes the enhanced electrochemical current response generated by a composite material consisting of gold nanoparticles (Au NPs) decorated on a metal-organic framework (MOF) containing iron and cobalt (FeCo). The Au NP-decorated FeCo-based MOF labeled with primary antibodies (Ab1) significantly enhances the electrochemical response, enabling accurate detection of AFP. Similarly, HRP-Au nanoprism (Au NPR) nanocomposites were prepared via a one-pot assembly, where horseradish peroxidase (HRP) and the secondary antibody (Ab2) were coimmobilized on Au NPRs to form a stable nanocomposite. The immunosensor was fabricated by assembling Au NPs@ FeCo-MOF and capture antibodies (Ab1) onto a glassy carbon electrode. The MOF served as a conductive matrix, AuNPs enhanced electron transfer, and Ab1 ensured specific antigen recognition. When the AFP antigen is present, labeled Ab2 binds to the Au NP-decorated FeCo-MOF via specific antigen-antibody interactions, leading to enhanced electrochemical signals for sensitive detection. The immunosensor response was measured by differential pulse voltammetry (DPV) in phosphate-buffered solution (PBS) containing hydrogen peroxide (H2O2) and 3,3',5,5'-tetramethylbenzidine (TMB). Under controlled conditions, the immunosensor exhibited a linear response to AFP over the range of 0.0001 to 100 ng mL-1, with a detection limit of 1.2 pg mL-1 (S/N = 3), indicating high sensitivity. The immunosensor's performance was validated by detecting AFP in human serum samples, demonstrating its potential for ultrasensitive detection of AFP and other biomarkers.

High-sensitivity viral diagnostics typically use PCR to detect and amplify viral nucleic acids which requires fluorescence reporters, enzymatic amplification, specialized equipment and can be time-consuming. In this work, we describe fuel-free (FF) Rolosense, a diagnostic approach that leverages mechanical force sensing as a fundamental transduction mechanism. We use the Brownian motion of aptamer-coated microparticles on an aptamer-modified surface for viral detection. The microparticles function as both the sensing and transduction elements, reporting specific molecular interactions where the presence of viral particles stalls their motion by cross-linking them to the surface. FF-Rolosense harnesses biased motion and thermal fluctuations to achieve rapid, sensitive, and specific detection of intact virions─the active agents of infection. This approach represents a fundamental shift from conventional diagnostic methods and demonstrates a limit of detection as low as 103 copies/mL for SARS-CoV-2 variants, including BA.1 and BA.5, and effectively differentiates SARS-CoV-2 from other viral pathogens such as Influenza A, HCoV OC43, and 229E. We also show that FF-Rolosense readout is amenable to deep learning analysis revealing single particle viral binding events. Finally, we demonstrate potential for point-of-care and home-based applications by using a 3D-printed brightfield microscope, Roloscope, for FF-Rolosense readout. Taken together, this work shows a complementary strategy for viral diagnostics that employs a mechanical mechanism of transduction.

Intrinsically disordered proteins (IDPs) rapidly interconvert between conformers, requiring an ensemble description. This complicates their experimental characterization, and force field limitations pose challenges for their simulation. Here, we use isotope-labeled and unlabeled infrared (IR) spectra to reweight simulated ensembles of the elastin-like peptide GVGVPGVG, a paradigmatic disordered peptide. By comparing the results obtained with different spectra, we explicitly show that the weights are underdetermined by the ensemble averaged data. We identify which labels and frequency regions maximize structural information while minimizing sensitivity to simulation error and show that these regions report on whether the peptide makes specific interactions. Our work shows the importance of incorporating simulations and simulated spectra at the planning stages of isotope-labeled IR experiments and more generally provides a framework for interpreting IR data for IDPs.

The large number and diversity of chemicals currently in use present significant challenges in assessing their human and environmental health risks due to a paucity of toxicological data. To address this shortage, high-throughput screening technologies are used to rapidly evaluate the toxicity of these chemicals. Suitable chemical libraries are crucial to evaluate the performance of these technologies and generate the cognate toxicity data. Unlike traditional chemical libraries designed for specific disease targets or receptor interactions, the PrecisionTox collection prioritizes diversity in targets and mechanisms of toxicity to ensure broad applicability in toxicity predictions to test the concept of phylotoxicology. Phylotoxicology proposes that mechanisms of toxicity are evolutionary conserved among distantly related species. Furthermore, the application of phylotoxicology can contribute to the reduction of mammalian species in toxicity testing. Here an approach for generating a chemical library based on chemical properties; physicochemical, biomolecular and toxicological; as well as practical considerations; including compound availability, cost, purity and shipping regulations is reported. From an initial pool of over 1,500 nominees, a set of 200 chemicals was selected based on multiple criteria, including organ toxicity, environmental exposure, structure, MoA and toxicological relevance. Additionally, information on baseline toxicity, Absorption, Distribution, Metabolism and Excretion (ADME) properties and utility for in vitro testing was collected. This work underscores the necessity of thoughtful chemical selection to refine toxicological models, improve hazard identification and support regulatory efforts to protect human and environmental health.

SUMOylation - a protein post-translational modification (PTM) related to ubiquitylation - involves the reversible covalent attachment of the small ubiquitin-like modifier (SUMO) to proteins. During the conjugation and deconjugation cycle, SUMO is recognised and positioned by various enzymes through specific non-covalent interactions. This review discusses the core interactions with the SAE2 subunit of the SUMOspecific heterodimeric E1 enzyme SAE1:SAE2, the SUMO E2 enzyme UBC9 and the SUMO-specific proteases of the SENP family and USPL1. We describe the evolutionary origins of these interactions and their structural basis; moreover, as SUMO:enzyme interactions are generally similar in their overall outline to those between ubiquitin and its specific enzymes, we highlight these similarities, as well as the differences. All of the mentioned interactions use a similar surface on SUMO, which is distinct from the groove that binds SUMO-interacting motifs (SIMs), meaning that while the enzyme interactions are mutually exclusive, each is compatible with simultaneous SIM binding. This review is accompanied by another in the same issue that focuses on interactions with SUMO E3 ligases and downstream effectors of SUMOylation, together providing comprehensive coverage of the non-covalent interactions formed by SUMO proteins.

Purpose Eye-tracking technology offers significant potential in healthcare by enabling hands-free interactions that reduce physical contact and infection transmission risks. However, its adoption remains suboptimal due to barriers including unfavorable cost-benefit perceptions, digital literacy gaps and workflow disruption concerns. This study explores value co-creation interactions between technology providers and healthcare professionals that facilitate eye-tracking adoption in digitalized healthcare settings. Design/methodology/approach The study employs a qualitative approach drawing on exploratory and semi-structured interviews with eye-tracking technology providers and physicians who use eye-tracking in clinical practice and research. Data analysis follows a thematic analysis approach. Findings The findings reveal two distinct but interconnected dimensions of value co-creation interactions that enable eye-tracking adoption. Value co-production-enabling interactions encompass aligning technology capabilities with user needs, co-developing manuals and guidelines and collaboratively interpreting regulatory frameworks. Value-in-use-enabling interactions focus on aligning technology performance with end-user experience, co-developing implementation strategies and collaborative data interpretation and analysis. Originality/value This study contributes to healthcare digitalization literature by examining how collaborative interactions between technology providers and healthcare professionals enable complex technology adoption. Unlike previous research focusing primarily on patient-provider relationships, this study demonstrates how technology providers actively participate in healthcare value chains beyond traditional product delivery. The findings extend value co-creation theory by identifying specific interaction mechanisms within value co-production and value-in-use dimensions, contributing to understanding how collaborative approaches may support hands-free healthcare technology integration.

Expression of the APX gene and ROS levels in four Gossypium species are interrelated, functioning in cotton pigment gland development and abiotic stress responses. Ascorbate peroxidases (APXs) represent a crucial family of antioxidant enzymes that play essential roles in plant responses to environmental stresses and the regulation of developmental processes. Pigment glands in cotton are specialized structures formed through programmed cell death (PCD), a process inherently linked to the accumulation of reactive oxygen species (ROS). Despite the well-established functions of APXs in maintaining ROS homeostasis and the recognized involvement of ROS in pigment gland development, the specific interactions between APXs and ROS within these glands remain largely uncharacterized. In this study, bioinformatics approaches were employed to systematically analyze APX genes across multiple cotton varieties. Expression profiling revealed that APX genes exhibited both upregulated and downregulated responses to environmental stresses as well as hydrogen peroxide (H2O2) treatment, suggesting a potential dual-function mechanism for APXs in regulating ROS levels. Significant accumulation of ROS was observed in glands, while negligible levels were detected in glandless cotton. Comparative analysis indicated that most APX genes displayed higher expression levels in glanded cotton plants. Functional validation experiments demonstrated that overexpression and knockdown of GhMYC2-like-a key regulator involved in pigment gland formation-respectively induced and repressed the expression of six APX genes. These findings suggest that members of the APX family are integral components within the regulatory network governing cotton pigment gland formation. This study not only provides novel insights into the role of APXs within cotton biology but also establishes a solid foundation for future investigations into their functions related to ROS-mediated processes.

Protein nanorotors control the size of lipid domains in phase-separated monolayers.

A series of pyrrolidine-2-carbonitrile derivatives was designed, synthesized, and evaluated for their antidiabetic potential. The synthesized compounds exhibited notable inhibitory activity, with IC₅₀ values ranging from 9.36 to 21.54 µg/mL for α-amylase, 13.32 to 46.14 µg/mL for α-glucosidase, and 22.87 to 42.12 µg/mL for DPP-IV. Among the evaluated derivatives, compounds bearing para-methyl (6b) and para-chloro (6c) substituents demonstrated the most potent inhibitory activity across all three enzymatic targets. To elucidate the underlying trends, a SAR analysis was conducted, revealing that both electronic properties and steric effects of the substituents significantly influenced enzyme inhibition potency. The molecular docking studies showed strong and specific interactions between the active compounds and key residues within the catalytic sites of the target enzymes. In addition, UV-visible absorption and fluorescence spectroscopy studies demonstrated high binding affinities for both 6b and 6c with HSA, having binding constant (Ka) values of 7.31 × 10⁵ M⁻¹ and 7.43 × 10⁵ M⁻¹, respectively. Taken together, these findings highlight compounds 6b and 6c as promising lead candidates for the development of multitarget antidiabetic agents.

Innovative design and synthesis of dual-acting hCA IX/CDK-2 inhibitors through hetero ring fused pyrimidine utilization for cutting-edge anticancer therapy: Zein nanoparticles for in vivo lung cancer treatment.

Integrated multi-tissue transcriptomics reveals cross-tissue regulatory networks and hub genes regulating feed efficiency in aging chicken.

ABSTRACTBackgroundPancreatic ductal adenocarcinoma (PDAC) is an exceptionally lethal malignancy, with high percents of patients presenting with liver metastases (LM). However, the mechanisms driving liver metastases remain critical bottlenecks requiring urgent exploration.ObjectiveTo identify the key cellular subsets driving PDAC liver metastases, elucidate their interactions with the metastatic microenvironment, and define the underlying mechanisms of liver colonization.Materials and MethodsIntegrated single‐cell transcriptomic analysis was performed using scRNA‐seq data of PT and LM. The expression of signature genes within the identified cell subset was validated using clinical samples from PDAC PT and LM patients. Furthermore, ligand‐receptor network analysis was conducted between the specific tumor cell subset and key immune cells.ResultsWe identified a novel liver‐enriched metastatic subset (LEMS), a terminally differentiated malignant cell subpopulation characterized by metabolic reprogramming and hyperactivation of immunosuppressive pathways. We further validated the LEMS signature genes, oxidized low‐density lipoprotein receptor 1 (OLR1) and solute carrier family 7 member 7 (SLC7A7), as potential diagnostic biomarkers for liver metastases. Importantly, we found that SPP1+ macrophages interacted with LEMS via ligand‐receptor networks, thereby driving invasion and immune evasion.DiscussionWe revealed the highly malignant features of LEMS and crosstalk between LEMS and SPP1+ macrophages in liver metastases. However, it is necessary to expand clinical cohorts and in vivo models to comprehensively elucidate the specific mechanistic interactions between LEMS and macrophages.ConclusionWe delineated LEMS as an enriched subset in LM and proposed targeting of LEMS‐SPP1+ macrophage interactions as a therapeutic strategy to disrupt metastatic progression.

Quantized topological phase of ultrasonic guided wave with spin orbit interaction.

Deciphering the specific intermolecular interactions for N, N-Dimethylacetamide with water at varying temperatures employing thermophysical and FTIR analysis

Leaflet-specific effects of charged lipids on a voltage-gated potassium channel.