1,720,986 research outputs found
From Clocks to Synchrony: The Design of Bioinspired Self‐Regulation in Chemical Systems
No full textFeedback plays a vital role in the self-regulation of processes that govern biological structure and function such as the switches, rhythms, and synchronized states that are observed in cells. This chapter discusses the mechanisms of feedback and nonequilibrium state selection in the bioinspired chemical systems. The language that has evolved through the study of self-organization in chemical systems extends across multiple disciplines, and scientists are becoming increasingly adept at engineering functional feedback in both chemical and biological systems for applications. In living systems, autocatalysis is used as a switch to initiate processes in response to chemical signals. The Belousov–Zhabotinsky reaction remains the only homogeneous system to display long-lived oscillations in closed batch reactor. One of the remarkable discoveries regarding single-celled organisms such as bacteria was their ability to display collective behavior and form multicellular communities. The simplest response of cells is synchronization of activity, driven by intercellular chemical communication and feedback in the signaling mechanism
Ester hydrolysis: Conditions for acid autocatalysis and a kinetic switch
Full text linkAutocatalysis can be used to obtain a sharp switch in state after a programmable time lag. Here, autocatalysis driven by acid concentration during the dissolution and hydrolysis of solid esters was investigated. In a generic model of the process, conditions were identified for observation of a kinetic switch with the introduction of an inhibitor species, bicarbonate, to delay the onset of autocatalysis. The kinetic profiles from the hydrolysis of two esters, d-gluconic acid δ-lactone and dl-lactide, were examined and evidence for dissolution-limited acid autocatalysis was obtained with lactide
Switches induced by quorum sensing in a model of enzyme-loaded microparticles
Full text linkQuorum sensing refers to the ability of bacteria and other single-celled organisms to respond to changes in cell density or number with population-wide changes in behaviour. Here, simulations were performed to investigate quorum sensing in groups of diffusively coupled enzyme microparticles using a well-characterized autocatalytic reaction which raises the pH of the medium: hydrolysis of urea by urease. The enzyme urease is found in both plants and microorganisms, and has been widely exploited in engineering processes. We demonstrate how increases in group size can be used to achieve a sigmoidal switch in pH at high enzyme loading, oscillations in pH at intermediate enzyme loading and a bistable, hysteretic switch at low enzyme loading. Thus, quorum sensing can be exploited to obtain different types of response in the same system, depending on the enzyme concentration. The implications for microorganisms in colonies are discussed, and the results could help in the design of synthetic quorum sensing for biotechnology applications such as drug delivery
Towards feedback-controlled nanomedicines for smart, adaptive delivery
No full textNanomedicines for controlled drug release provide temporal and spatial regulation of drug bioavailability in the body. The timing of drug release is usually engineered either for slow gradual release over an extended period of time or for rapid release triggered by a specific change in its physicochemical environment. However, between these two extremes, there is the desirable possibility of adaptive nanomedicines that dynamically modulate drug release in tune with its changing environment. Adaptation and response through communication with its environment is a fundamental trait of living systems; therefore, the design of biomimetic nanomedicines through the approaches of bottom-up synthetic biology provides a viable route to this goal. This could enable drug delivery systems to optimize release in synchronicity with the body’s natural biological rhythms and the personalized physiological characteristics of the patient, e.g. their metabolic rate. Living systems achieve this responsiveness through feedback-controlled biochemical processes that regulate their functional outputs. Towards this goal of adaptive drug delivery systems, we review the general benefits of nanomedicine formulations, provide existing examples of experimental nanomedicines that encapsulate the metabolic function of enzymes, and give relevant examples of feedback-controlled chemical systems. These are the underpinning concepts that hold promise to be combined to form novel adaptive release systems. Furthermore, we motivate the advantages of adaptive release through chronobiological examples. By providing a brief review of these topics and an assessment of the state of the art, we aim to provide a useful resource to accelerate developments in this field
Modelling bacteria-inspired dynamics with networks of interacting chemicals
Full text linkOne approach to understanding how life-like properties emerge involves building synthetic cellular systems that mimic certain dynamical features of living cells such as bacteria. Here, we developed a model of a reaction network in a cellular system inspired by the ability of bacteria to form a biofilm in response to increasing cell density. Our aim was to determine the role of chemical feedback in the dynamics. The feedback was applied through the enzymatic rate dependence on pH, as pH is an important parameter that controls the rates of processes in cells. We found that a switch in pH can be used to drive base-catalyzed gelation or precipitation of a substance in the external solution. A critical density of cells was required for gelation that was essentially independent of the pH-driven feedback. However, the cell pH reached a higher maximum as a result of the appearance of pH oscillations with feedback. Thus, we conclude that while feedback may not play a vital role in some density-dependent behavior in cellular systems, it nevertheless can be exploited to activate internally regulated cell processes at low cell densities
Influence of oxygen on chemoconvective patterns in the iodine clock reaction
Full text linkThere is increasing interest in using chemical clock reactions to drive material formation; however, these reactions are often subject to chemoconvective effects, and control of such systems remains challenging. Here, we show how the transfer of oxygen at the air–water interface plays a crucial role in the spatiotemporal behavior of the iodine clock reaction with sulfite. A kinetic model was developed to demonstrate how the reaction of oxygen with sulfite can control a switch from a low-iodine to high-iodine state under well-stirred conditions and drive the formation of transient iodine gradients in unstirred solutions. In experiments in thin layers with optimal depths, the reaction couples with convective instability at the air–water interface forming an extended network-like structure of iodine at the surface that develops into a spotted pattern at the base of the layer. Thus, oxygen drives the spatial separation of iodine states essential for patterns in this system and may influence pattern selection in other clock reaction systems with sulfite
Exploitation of Feedback in Enzyme-catalysed Reactions
Full text linkSome cellular systems, such as yeast, bacteria and slime mould, display dynamic behavior including switches and rhythms driven by feedback in enzyme-catalysed reactions. The mechanisms of these processes have been well investigated and recent attention has turned to generating similar responses in synthetic biocatalytic systems, with a view to creating bioinspired analogues for applications. Here we discuss how feedback arises in the reaction mechanisms of some enzyme-catalyzed reactions invitro, the behaviour obtained and the emerging applications. These autocatalytic reactions may provide insights into behaviour in cellular systems as well as new methods for drug delivery, sensing and repair that can be exploited in living systems
Design of oscillatory dynamics in numerical simulations of compartment-based enzyme systems
No full textEnzymatic reactions that yield non-neutral products are known to involve feedback due to the bell-shaped pH-rate curve of the enzyme. Compartmentalizing the reaction has been shown to lead to transport-driven oscillations in theory; however, there have been few reproducible experimental examples. Our objective was to determine how the conditions could be optimized to achieve pH oscillations. We employed numerical simulations to investigate the hydrolysis of ethyl acetate in a confined esterase enzyme system, examining the influence of key factors on its behavior. Specific parameter ranges that lead to bistability and self-sustained pH oscillations and the importance of fast base transport for oscillations in this acid-producing system are highlighted. Suggestions are made to expand the parameter space for the occurrence of oscillations, including modifying the maximum of the enzyme pH-rate curve and increasing the negative feedback rate. This research not only sheds light on the programmable nature of enzyme-driven pH regulation but also furthers knowledge on the optimal design of such feedback systems for experimentalists
MODELLING OF NON-EQUILIBRIUM SYSTEMS: REACTION NETWORKS FOR BIOINSPIRED BEHAVIOUR
No full textThe following sections are included:My View of the Present State of Research on Modelling of Non-equilibrium SystemsMy Research Contributions to Modelling of Non-equilibrium SystemsOutlook on Future Developments of Research on Modeling of Non-equilibrium SystemsReference
A novel high-throughput ex vivo ovine skin wound model for testing emerging antibiotics
Full text linkThe development of antimicrobials is an expensive process with increasingly low success rates, which makes further investment in antimicrobial discovery research less attractive. Antimicrobial drug discovery and subsequent commercialization can be made more lucrative if a fail-fast-and-fail-cheap approach can be implemented within the lead optimization stages where researchers have greater control over drug design and formulation. In this article, the setup of an ex vivo ovine wounded skin model infected with Staphylococcus aureus is described, which is simple, cost-effective, high throughput, and reproducible. The bacterial physiology in the model mimics that during infection as bacterial proliferation is dependent on the pathogen's ability to damage the tissue. The establishment of wound infection is verified by an increase in viable bacterial counts compared to the inoculum. This model can be used as a platform to test the efficacy of emerging antimicrobials in the lead optimization stage. It can be contended that the availability of this model will provide researchers developing antimicrobials with a fail-fast-and-fail-cheap model, which will help increase success rates in subsequent animal trials. The model will also facilitate the reduction and refinement of animal use for research and ultimately enable faster and more cost-effective translation of novel antimicrobials for skin and soft tissue infections to the clinic
- …
