Explore the vast range of titles available.

Constructing artificial systems that effectively replace or supplement natural biological machinery within cells is one of the fundamental challenges underpinning bioengineering. At the sub‐cellular scale, artificial organelles (AOs) have significant potential as long‐acting biomedical implants, mimicking native organelles by conducting intracellularly compartmentalized enzymatic actions. The potency of these AOs can be heightened when judiciously combined with genetic engineering, producing highly tailorable biohybrid cellular systems. Here, the authors present a cost‐effective, microliter scale (10 µL) polymersome (PSome) synthesis based on polymerization‐induced self‐assembly for the in situ encapsulation of Gaussia luciferase (GLuc), as a model luminescent enzyme. These GLuc‐loaded PSomes present ideal features of AOs including enhanced enzymatic resistance to thermal, proteolytic, and intracellular stresses. To demonstrate their biomodulation potential, the intracellular luminescence of GLuc‐loaded PSomes is coupled to optogenetically engineered cardiomyocytes, allowing modulation of cardiac beating frequency through treatment with coelenterazine (CTZ) as the substrate for GLuc. The long‐term intracellular stability of the luminescent AOs allows this cardiostimulatory phenomenon to be reinitiated with fresh CTZ even after 7 days in culture. This synergistic combination of organelle‐mimicking synthetic materials with genetic engineering is therefore envisioned as a highly universal strategy for the generation of new biohybrid cellular systems displaying unique triggerable properties. Herein, the authors present a microliter scale synthesis of enzyme‐loaded polymersomes based on polymerization‐induced self‐assembly as a versatile approach for fabricating highly robust artificial organelles (AOs). The luminescence of encapsulated luciferase is highly resistant to thermal, proteolytic, and intracellular stresses allowing these AOs to show cardiostimulatory effects in optogenetically modified induced pluripotent stem cell‐derived cardiomyocytes even after a week in vitro.

The circadian rhythm generates out-of-equilibrium metabolite oscillations that are controlled by feedback loops under light/dark cycles. Here we describe a non-equilibrium nanosystem comprising a binary population of enzyme-containing polymersomes capable of light-gated chemical communication, controllable feedback and coupling to macroscopic oscillations. The populations consist of esterase-containing polymersomes functionalized with photo-responsive donor–acceptor Stenhouse adducts (DASA) and light-insensitive semipermeable urease-loaded polymersomes. The DASA–polymersome membrane becomes permeable under green light, switching on esterase activity and decreasing the pH, which in turn initiates the production of alkali in the urease-containing population. A pH-sensitive pigment that absorbs green light when protonated provides a negative feedback loop for deactivating the DASA–polymersomes. Simultaneously, increased alkali production deprotonates the pigment, reactivating esterase activity by opening the membrane gate. We utilize light-mediated fluctuations of pH to perform non-equilibrium communication between the nanoreactors and use the feedback loops to induce work as chemomechanical swelling/deswelling oscillations in a crosslinked hydrogel. We envision possible applications in artificial organelles, protocells and soft robotics.The circadian rhythm generates out-of-equilibrium metabolite oscillations controlled by feedback loops under light/dark cycles. Now, it has been shown that these life-like properties can emerge from a non-equilibrium nanosystem comprising a binary population of enzyme-containing polymersomes capable of light-gated chemical communication, controllable feedback and coupling to macroscopic oscillations.

Methods to diagnose malaria are of paramount interest to eradicate the disease. Current methods have severe limitations, as they are either costly or not sensitive enough to detect low levels of parasitemia. Here we report an ultrasensitive, yet low-resource chemical assay for the detection and quantification of hemozoin, a biomarker of all Plasmodium species. Solubilized hemozoin catalyzes the atom transfer radical polymerization of N -isopropylacrylamide above the lower critical solution temperature of poly( N -isopropylacrylamide). The solution becomes turbid, which can be observed by naked eye and quantified by UV-visible spectroscopy. The rate of turbidity increase is proportional to the concentration of hemozoin, with a detection limit of 0.85 ng mL −1 . Malaria parasites in human blood can be detected down to 10 infected red blood cells μL −1 . The assay could potentially be applied as a point-of-care test. The signal-amplification of an analyte by biocatalytic precipitation polymerization represents a powerful approach in biosensing. Methods to diagnose malaria are of interest but can be costly or not sensitive enough to detect low levels of parasitemia. Here the authors report an ultrasensitive method by using hemozoin (a biomarker of all Plasmodium species) to catalyse the polymerization of N-isopropylacrylamide.

Biological systems integrate multiple feedback processes to regulate their adaptation to evolving stimuli with high specificity. Inspired by wavelength-selective feedback processes in visual signaling, we present a synthetic nanoreactor system capable of producing orthogonal, wavelength-dependent positive and negative feedback loops. Polymersomes functionalized with a broad-spectrum pyrazolone-based Donor-Acceptor Stenhouse Adduct (DASA) encapsulate an esterase enzyme and undergo light-gated permeability switching. Upon irradiation, the nanoreactors operate out-of-equilibrium, hydrolyzing ethyl acetate to generate acetic acid in a wavelength-programmed manner. Under yellow light (590 nm), positive feedback is mediated by spectral unmasking: acid-induced protonation of a solubilized dye decreases competition for yellow light, enhancing membrane permeability and enzyme activity, yielding a positive feedback loop. In contrast, blue light (405 nm) irradiation leads to the accumulation of the same dye that spectrally competes with the photoswitch, progressively suppressing membrane permeability by formation of a negative feedback loop. These stimulus-specific feedback dynamics enable reversible and tunable control over enzymatic reaction kinetics. Importantly, this platform introduces a paradigm shift for light-programmed, autonomous regulation in synthetic cell mimics and could open a pathway to dynamic modulation of microscale environments and biointerfaces without genetic intervention.

Infectious diseases continue to pose a substantial burden on global populations, requiring innovative broad-spectrum prophylactic and treatment alternatives. Here, we have designed modular synthetic polymer nanoparticles that mimic functional components of host cell membranes, yielding multivalent nanomimics that act by directly binding to varied pathogens. Nanomimic blood circulation time was prolonged by reformulating polymer–lipid hybrids. Femtomolar concentrations of the polymer nanomimics were sufficient to inhibit herpes simplex virus type 2 (HSV-2) entry into epithelial cells, while higher doses were needed against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given their observed virustatic mode of action, the nanomimics were also tested with malaria parasite blood-stage merozoites, which lose their invasive capacity after a few minutes. Efficient inhibition of merozoite invasion of red blood cells was demonstrated both in vitro and in vivo using a preclinical rodent malaria model. We envision these nanomimics forming an adaptable platform for developing pathogen entry inhibitors and as immunomodulators, wherein nanomimic-inhibited pathogens can be secondarily targeted to sites of immune recognition.

Two photon polymerization (2PP) 3D printing enables top-down biomaterial synthesis with nanoscale spatial resolution for de novo design of monodisperse injectable drug delivery systems. To address the limitations of current 2PP resins, we developed Spatiotemporal Controlled Release Inks of Biocompatible polyEsters (SCRIBE), a novel poly(lactic-co-glycolic acid)-triacrylate resin family with sub-micron resolution and tuneable hydrolysis. SCRIBE enables direct printing of hollow microparticles with tuneable chemistry and complex geometries inaccessible to molding techniques, which we use to engineer controlled protein release in vitro and in vivo. We use SCRIBE microparticles to modulate antibody titers and class switching as a function of antigen release rate and extend these findings to enable a single-injection vaccine formulation with extended antibody induction kinetics. Demonstrating how the chemistry and CAD of 2PP-printed microparticles can be used to tune responses to biomacromolecule release in vivo opens significant opportunities for a new generation of drug delivery vehicles. biorxiv;2024.10.02.616252v1/UFIG1F1ufig1