Chemical Cascading Between Polymersomal Nanoreactor Populations

[EN] Harnessing interactions of functional nano-compartments to generate larger particle assemblies allows studying diverse biological behaviors based on their population states and can lead to the development of smart materials. Herein, thiol-functionalized polymersome nanoreactors are utilized as responsive organelle-like nano-compartments-with inherent capacity to associate into larger aggregates in response to change in the redox state of their environment-to study the kinetics of cascade reactions and explore functions of their collective under different population states. Two nanoreactor populations, glucose oxidase- and horseradish peroxidase-loaded polymersomes, are prepared, and the results of their cascading upon addition of glucose are investigated. The kinetics of resorufin production in associated polymersomes and non-associated polymersome populations are compared, observing a decreased rate upon association. For the associated populations, faster chemical cascading is found when the two types of nanoreactors are associated in a concerted step, as compared to sequential association. The addition of competing agents such as catalase impacts the communication between non-associated polymersomes, whereas such an effect is less pronounced for the associated ones. Altogether, the results showcase the impact of collective associations on enzymatic cascading between organelle-like nanoreactors.Y.A. and A.L.-L. contributed equally to this work. The authors would like to acknowledge the support from the Dutch Ministry of Education, Culture, and Science (Gravitation program 024.001.035 and Spinoza premium) and the ERC Advanced Grant (Artisym 694120).A.L.-L. acknowledges support from the MSCA Cofund project oLife, which has received funding from the European Union's Horizon 2020 research and innovation program under the Grant Agreement 847675; and the Maria Zambrano Program from the Spanish Government funded by NextGenerationEU from the European Union. Dr. Imke Pijpers is thanked for cryo-TEM imaging. Dr. Pascal Welzen is acknowledged for advice and useful discussion on polymer and polymersome preparation.Altay, Y.; Llopis-Lorente, A.; Abdelmohsen, LKEA.; Van Hest, JC. (2023). Chemical Cascading Between Polymersomal Nanoreactor Populations. Macromolecular Chemistry and Physics. 224(1):1-5. https://doi.org/10.1002/macp.20220026915224

Cucurbit-Like Polymersomes with Aggregation-Induced Emission Properties Show Enzyme-Mediated Motility

Polymersomes that incorporate aggregation-induced emission (AIE) moieties are attractive inherently fluorescent nanoparticles with biomedical application potential for cell/tissue imaging and tracking, as well as phototherapeutics. An intriguing feature that has not been explored yet is their ability to adopt a range of asymmetric morphologies. Structural asymmetry allows nanoparticles to be exploited as active (motile) systems. Here, we present the design and preparation of AIE fluorophore integrated (AIEgenic) cucurbit-shaped polymersome nanomotors with enzyme-powered motility. The cucurbit scaffold was constructed via morphology engineering of biodegradable fluorescent AIE-polymersomes, followed by functionalization with enzymatic machinery via a layer-by-layer (LBL) self-assembly process. Because of the enzyme-mediated decomposition of chemical fuel on the cucurbit-like nanomotor surface, enhanced directed motion was attained, when compared with the spherical counterparts. These cucurbit-shaped biodegradable AIE-nanomotors provide a promising platform for the development of active delivery systems with potential for biomedical applications

Spatiotemporal Communication in Artificial Cell Consortia for Dynamic Control of DNA Nanostructures

[EN] The spatiotemporal orchestration of cellular processes is a ubiquitous phenomenon in pluricellular organisms and bacterial communities, where sender cells secrete chemical signals that activate specific pathways in distant receivers. Despite its importance, the engineering and investigation of spatiotemporal communication in artificial cell consortia remains underexplored. In this study, we present spatiotemporal communication between cellular-scale entities acting as both senders and receivers. The transmitted signals are leveraged to elicit conformational alterations within compartmentalized DNA structures. Specifically, sender entities control and generate diffusive chemical signals, namely, variations in pH, through the conversion of biomolecular inputs. In the receiver population, compartmentalized DNA nanostructures exhibit changes in conformation, transitioning between triplex and duplex assemblies, in response to this pH variation. We demonstrate the temporal regulation of activated DNA nanostructures through the coordinated action of two antagonistic sender populations. Furthermore, we illustrate the transient distance-dependent activation of the receivers, facilitated by sender populations situated at defined spatial locations. Collectively, our findings provide novel avenues for the design of artificial cell consortia endowed with programmable spatiotemporal dynamics through chemical communication.The authors would like to acknowledge the support from the Dutch Ministry of Education, Culture, and Science (Gravitation programs 024.001.035, 024.003.013, 024.005.020 - Interactive Polymer Materials IPM, and the Spinoza premium), ERC Advanced Grant (Artisym 694120), ERC Advanced Grant Edison (101052997), the Spanish Ministry of Science and Innovation, AEI, and FEDER-EU (project PID2021-126304OB-C41), and the GVA (Project CIPROM/2021/007). A.L.-L. acknowledges support from the MSCA Cofund project oLife, which has received funding from the European Union's Horizon 2020 research and innovation program under the Grant Agreement 847675. A.L.-L. thanks the Spanish Government for his "Ramon y Cajal" Fellowship (RYC2021-034728-I), funded by MCIN/AEI/10.13039/501100011033 and by the European Union >/>. A.L-L. also thanks the UPV for funding (Ayuda para potenciar la investigacion postdoctoral de la UPV (PAID-PD-22), Ayuda a Primeros Proyectos de Investigacion (PAID-06-22), Vicerrectorado de Investigacion de la Universitat Politecnica de Valencia (UPV)).Llopis-Lorente, A.; Shao, J.; Ventura-Cobos, J.; Buddingh, BC.; Martínez-Máñez, R.; Van Hest, JCM.; Abdelmohsen, LKEA. (2024). Spatiotemporal Communication in Artificial Cell Consortia for Dynamic Control of DNA Nanostructures. ACS CENTRAL SCIENCE. 10(8):1619-1628. https://doi.org/10.1021/acscentsci.4c007021619162810

Formation of Well-Defined, Functional Nanotubes via Osmotically Induced Shape Transformation of Biodegradable Polymersomes

Contains fulltext : 161997.pdf (publisher's version ) (Open Access

Engineering transient dynamics of artificial cells by stochastic distribution of enzymes

Here the authors develop a coacervate micromotor that can display autonomous motion as a result of stochastic distribution of propelling units. This stochastic-induced mobility is validated and explained through experiments and theory. Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors

Legislative History: An Act To Amend the Harness Racing Laws Regarding Distributions from the Fund to Supplement Harness Racing Purses (SP786)(LD 2042)

https://digitalmaine.com/legishist122/3041/thumbnail.jp

Adaptive polymeric assemblies for applications in biomimicry and nanomedicine

Dynamic and adaptive self-assembly systems are able to sense an external or internal (energy or matter) input and respond via chemical or physical property changes. Nanomaterials that show such transient behavior have received increasing interest in the field of nanomedicine due to improved spatiotemporal control of the nanocarrier function. In this regard, much can be learned from the field of systems chemistry and bottom-up synthetic biology, in which complex and intelligent networks of nanomaterials are designed that show transient behavior and function to advance our understanding of the complexity of living systems. In this Perspective, we highlight the recent advancements in adaptive nanomaterials used for nanomedicine and trends in transient responsive self-assembly systems to envisage how these fields can be integrated for the formation of next-generation adaptive stimuli-responsive nanocarriers in nanomedicine

Morphology Under Control: Engineering Biodegradable Stomatocytes

Biodegradable nanoarchitectures, with well-defined morphological features, are of great importance for nanomedical research; however, understanding (and thereby engineering) their formation is a substantial challenge. Herein, we uncover the supramolecular potential of PEG–PDLLA copolymers by exploring the physicochemical determinants that result in the transformation of spherical polymersomes into stomatocytes. To this end, we have engineered blended polymersomes (comprising copolymers with varying lengths of PEG), which undergo solvent-dependent reorganization inducing negative spontaneous membrane curvature. Under conditions of anisotropic solvent composition across the PDLLA membrane, facilitated by the dialysis methodology, we demonstrate osmotically induced stomatocyte formation as a consequence of changes in PEG solvation, inducing negative spontaneous membrane curvature. Controlled formation of unprecedented, biodegradable stomatocytes represents the unification of supramolecular engineering with the theoretical understanding of shape transformation phenomena

Engineering transient dynamics of artificial cells by stochastic distribution of enzymes

Random fluctuations are inherent to all complex molecular systems. Although nature has evolved mechanisms to control stochastic events to achieve the desired biological output, reproducing this in synthetic systems represents a significant challenge. Here we present an artificial platform that enables us to exploit stochasticity to direct motile behavior. We found that enzymes, when confined to the fluidic polymer membrane of a core-shell coacervate, were distributed stochastically in time and space. This resulted in a transient, asymmetric configuration of propulsive units, which imparted motility to such coacervates in presence of substrate. This mechanism was confirmed by stochastic modelling and simulations in silico. Furthermore, we showed that a deeper understanding of the mechanism of stochasticity could be utilized to modulate the motion output. Conceptually, this work represents a leap in design philosophy in the construction of synthetic systems with life-like behaviors