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Register a new userEnzyme-Based Logic Analysis of Biomarkers at Physiological Concentrations: AND Gate with Double-Sigmoid Filter Response
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We report the first realization of a biomolecular AND gate function with double-sigmoid response (sigmoid in both inputs). Two enzyme biomarker inputs activate the gate output signal which can then be used as indicating liver injury, but only when both of these inputs have elevated pathophysiological concentrations, effectively corresponding to logic-1 of the binary gate functioning. At lower, normal physiological concentrations, defined as logic-0 inputs, the liver-injury output levels are not obtained. High-quality gate functioning in handling of various sources of noise, on time scales of relevance to potential applications is enabled by utilizing filtering effected by a simple added biocatalytic process. The resulting gate response is sigmoid in both inputs when proper system parameters are chosen, and the gate properties are theoretically analyzed within a model devised to evaluate its noise-handling properties.
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The first realization of a biomolecular OR gate function with double-sigmoid response (sigmoid in both inputs) is reported. Two chemical inputs activate the enzymatic gate processes resulting in the output signal: chromogen oxidation, which occurs when either one of the inputs or both are present (corresponding to the OR binary function), and can be optically detected. High-quality gate functioning in handling of sources of noise is enabled by filtering involving pH control with an added buffer. The resulting gate response is sigmoid in both inputs when proper system parameters are chosen, and the gate properties are theoretically analyzed within a model devised to evaluate its noise-handling properties.
We report a study of a system which involves an enzymatic cascade realizing an AND logic gate, with an added photochemical processing of the output allowing to make the gates response sigmoid in both inputs. New functional forms are developed for quantifying the kinetics of such systems, specifically designed to model their response in terms of signal and information processing. These theoretical expressions are tested for the studied system, which also allows us to consider aspects of biochemical information processing such as noise transmission properties and control of timing of the chemical and physical steps.
We report the first systematic study of designed two-input biochemical systems as information processing gates with favorable noise-transmission properties accomplished by modifying the gates response from convex shape to sigmoid in both inputs. This is realized by an added chemical filter process which recycles some of the output back into one of the inputs. We study a system involving the biocatalytic function of the enzyme horseradish peroxidase, functioning as an AND gate. We consider modularity properties, such as the use of three different input chromogens that, when oxidized yield signal-detection outputs for various ranges of the primary input, hydrogen peroxide. We also examine possible uses of different filter-effect chemicals (reducing agents) to induce the sigmoid-response. A modeling approach is developed and applied to our data, allowing us to describe the enzymatic kinetics in the framework of a formulation suitable for evaluating the noise-handling properties of the studied systems as logic gates for information processing steps.
Solutions of manually purified gastric mucins have been shown to be promising lubricants for biomedical purposes, where they can efficiently reduce friction and wear. However, so far, such mucin solutions have been mostly tested in specific settings, and variations in the composition of the lubricating fluid have not been systematically explored. We here fill this gap and determine the viscosity, adsorption behavior, and lubricity of porcine gastric mucin solutions on hydrophobic surfaces at different pH levels, mucin and salt concentrations and in the presence of other proteins. We demonstrate that mucin solutions provide excellent lubricity even at very low concentrations of 0.01 % (w/v), over a broad range of pH levels and even at elevated ionic strength. Furthermore, we provide mechanistic insights into mucin lubricity, which help explain how certain variations in physiologically relevant parameters can limit the lubricating potential of mucin solutions. Our results motivate that solutions of manually purified mucin solutions can be powerful biomedical lubricants, e.g. serving as eye drops, mouth sprays or as a personal lubricant for intercourse.
Processes involving multi-input multi-step reaction cascades are used in developing novel biosensing, biocomputing, and decision making systems. In various applications different changes in responses of the constituent processing steps (reactions) in a cascade are desirable in order to allow control of the systems response. Here we consider conversion of convex response to sigmoid by intensity filtering, as well as threshold filtering, and we offer a general overview of this field of research. Specifically, we survey rate equation modelling that has been used for enzymatic reactions. This allows us to design modified biochemical processes as network components with responses desirable in applications.
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