Two-dimensional MoS 2 nanosheets (2D-MoS 2 ) have been widely used in many biological applications due to their distinctive physicochemical properties. Further, the development of surface modification using thiolated ligands allows us to use them for many specific applications. But the effect of possible ligand exchange on 2D-MoS 2 has never been explored, which can play an important role in diverse biological applications. In this study, we have observed the ligand-exchange phenomenon on 2D-MoS 2 in the presence of different thiolated ligands. The initial study proceeded with boron-dipyrromethene (BODIPY) functionalized MoS 2 with different concentrations of glutathione (GSH), which is the most abundant thiol species in the cytoplasm of various cancer cells. It was found that in the presence of GSH the fluorescence of BODIPY can be regenerated, which is time and concentration dependent. We have also examined this phenomenon with different thiol ligands and transition-metal dichalcogenides (TMDs). We observed a variable rate of ligand exchange in different solvents, surface functionality, and receptor environments that helped us to construct sensor arrays. Interestingly, a ligand-exchange process was not observed in the presence of dithiols. Further, this concept was applied to a cancerous cell line for in vitro delivery. We found that BODIPY-functionalized 2D-MoS 2 undergoes thiol exchange by intracellular GSH and subsequently enhanced the fluorescence in the cytoplasm of cancer cells. This strategy can be applied to the development of 2D-TMD-based materials for various biological applications related to ligand exchange.

Analytical methods for detecting neurotransmitters (NTs) and organophosphorus (OP) pesticides with high sensitivity are vitally necessary for the rapid identification of physical, mental, and neurological illnesses, as well as to ensure food safety and safeguard ecosystems. In this work, we developed a supramolecular self-assembled system (SupraZyme) that exhibits multi-enzymatic activity. SupraZyme possesses the ability to show both oxidase and peroxidase-like activity, which has been employed for biosensing. The peroxidase-like activity was used for the detection of catecholamine NTs, epinephrine (EP), and norepinephrine (NE) with a detection limit of 6.3 µM and 1.8 µM, respectively, while the oxidase-like activity was utilized for the detection of organophosphate pesticides. The detection strategy for OP chemicals was based on the inhibition of acetylcholine esterase (AChE) activity: a key enzyme that is responsible for the hydrolysis of acetylthiocholine (ATCh). The corresponding limit of detection of paraoxon-methyl (POM) and methamidophos (MAP) was measured to be 0.48 ppb and 15.8 ppb, respectively. Overall, we report an efficient supramolecular system with multiple enzyme-like activities that provide a versatile toolbox for the construction of sensing platforms for the colorimetric point-of-care detection of both NTs and OP pesticides.

Regulation of enzyme activity and biocatalytic cascades on compartmentalized cellular components is key to the adaptation of cellular processes such as signal transduction and metabolism in response to varying external...

Regulation of enzyme activity is key to the adaptation of cellular processes such as signal transduction and metabolism in response to varying external conditions. Synthetic molecular glues have provided effective systems for enzyme inhibition and regulation of protein-protein interactions. So far, all the molecular glue systems based on covalent interactions operated in equilibrium conditions. To emulate dynamic far-from-equilibrium biological processes, we introduce herein a transient supramolecular glue with controllable lifetime. The transient system uses multivalent supramolecular interactions between guanidium group-bearing surfactants and adenosine triphosphates (ATP), resulting in bilayer vesicle structures. Unlike the conventional fuels for non-equilibrium assemblies, ATP here plays the dual role of providing a structural component for the assembly as well as presenting active functional groups to “glue” enzymes on the surface. While gluing of the enzymes on the vesicles achieves augmented catalysis, oscillation of ATP concentration allows temporal control of the catalytic activities. We further demonstrate temporal activation and control of biocatalytic cascade networks on the vesicles, which represents an essential cellular component. Altogether, the temporal activation of biocatalytic cascades on the dissipative vesicular glue presents an adaptable and dynamic system emulating heterogeneous cellular processes, opening up avenues for effective protocell construction and therapeutic interventions.

Alkaline phosphatase (ALP) is an important protein responsible for various conditions related to hepatobiliary, osteopenia, pregnancy, and certain cancers. Developing an easy-to-use paper-based sensor for ALP would provide a point-of-care diagnostic device. A silver-coordinated cytidine hydrogel is a potential candidate to show responses under different concentrations of ALP. Herein, we prepared and characterized a three-component hydrogel system comprising cytidine, boric acid, and silver nitrate. The gelation occurs rapidly within a minute at room temperature and atmospheric pressure, which makes the system more convenient to use. Reduction of Ag+ by the in situ generated ascorbic acid by ALP allows the development of colorimetric sensor based on the gel-coated paper, enabling quantification of ALP concentration. This portable sensor works efficiently on a smartphone color-scanning app, making point-of-care detection easier. RGB values obtained from scanning indicate the ALP concentration in the range of 1-100 nM, which is independent of mobile cameras. The hydrogel exhibits excellent solvo-reversibility and enables naked-eye colorimetric detection of ALP with a detection limit of 0.23 nM (0.016 U/L). The sensing strategy works well in spiked human serum with a detection limit of 0.34 nM (0.023 U/L) in solution and paper-based sensors. Overall, the cytidine-based gel system presents an effective point-of-care diagnostic system for detecting ALP with high sensitivity.