arXiv subjects

Evgeny Katz

Publications and source records attributed to Evgeny Katz.

At least 19 recordsLinked to original sources

arXiv2016

Diffusion of Oligonucleotides from within Iron-Crosslinked Polyelectrolyte-Modified Alginate Beads: A Model System for Drug Release

We developed and experimentally verified an analytical model to describe diffusion of oligonucleotides from stable hydrogel beads. The synthesized alginate beads are Fe3+-cross-linked as well as polyelectrolyte-doped for uniformity and stability at physiological pH. Data on diffusion of oligonucleotides from inside the beads provide physical insights into the volume nature of the immobilization of a fraction of oligonucleotides due to polyelectrolyte cross-linking, i.e., the absence of the surface-layer barrier in this case. Furthermore, our results suggest a new simple approach to measuring the diffusion coefficient of the mobile oligonucleotide molecules inside hydrogel. The considered alginate beads provide a model for a well-defined component in drug release systems and for the oligonucleotide-release transduction steps in drug-delivering and biocomputing applications. This is illustrated by destabilizing the beads with citrate that induces full oligonucleotide release with non-diffusional kinetics.

cond-mat.soft↗

arXiv2014

Kinetic Model for a Threshold Filter in an Enzymatic System for Bioanalytical and Biocomputing Applications

A recently experimentally observed biochemical "threshold filtering" mechanism by processes catalyzed by the enzyme malate dehydrogenase is explained in terms of a model that incorporates an unusual mechanism of inhibition of this enzyme that has a reversible mechanism of action. Experimental data for a system in which the output signal is produced by biocatalytic processes of the enzyme glucose dehydrogenase are analyzed to verify the model's validity. We also establish that fast reversible conversion of the output product to another compound, without the additional inhibition, cannot on its own result in filtering.

q-bio.MN↗

arXiv2014

Can bio-inspired information processing steps be realized as synthetic biochemical processes?

We consider possible designs and experimental realiza-tions in synthesized rather than naturally occurring bio-chemical systems of a selection of basic bio-inspired information processing steps. These include feed-forward loops, which have been identified as the most common information processing motifs in many natural pathways in cellular functioning, and memory-involving processes, specifically, associative memory. Such systems should not be designed to literally mimic nature. Rather, we can be guided by nature's mechanisms for experimenting with new information/signal processing steps which are based on coupled biochemical reactions, but are vastly simpler than natural processes, and which will provide tools for the long-term goal of understanding and harnessing nature's information processing paradigm. Our biochemical processes of choice are enzymatic cascades because of their compatibility with physiological processes in vivo and with electronics (e.g., electrodes) in vitro allowing for networking and interfacing of enzyme-catalyzed processes with other chemical and biochemical reactions. In addition to designing and realizing feed-forward loops and other processes, one has to develop approaches to probe their response to external control of the time-dependence of the input(s), by measuring the resulting time-dependence of the output. The goal will be to demonstrate the expected features, for example, the delayed response and stabilizing effect of the feed-forward loops.

q-bio.MN↗

arXiv2014

Notes on stochastic (bio)-logic gates: the role of allosteric cooperativity

Recent experimental breakthroughs have finally allowed to implement in-vitro reaction kinetics (the so called {\em enzyme based logic}) which code for two-inputs logic gates and mimic the stochastic AND (and NAND) as well as the stochastic OR (and NOR). This accomplishment, together with the already-known single-input gates (performing as YES and NOT), provides a logic base and paves the way to the development of powerful biotechnological devices. The investigation of this field would enormously benefit from a self-consistent, predictive, theoretical framework. Here we formulate a complete statistical mechanical description of the Monod-Wyman-Changeaux allosteric model for both single and double ligand systems, with the purpose of exploring their practical capabilities to express logical operators and/or perform logical operations. Mixing statistical mechanics with logics, and quantitatively our findings with the available biochemical data, we successfully revise the concept of cooperativity (and anti-cooperativity) for allosteric systems, with particular emphasis on its computational capabilities, the related ranges and scaling of the involved parameters and its differences with classical cooperativity (and anti-cooperativity).

cond-mat.dis-nn↗

arXiv2013

Networked Enzymatic Logic Gates with Filtering: New Theoretical Modeling Expressions and Their Experimental Application

We report the first study of a network of connected enzyme-catalyzed reactions, with added chemical and enzymatic processes that incorporate the recently developed biochemical filtering steps into the functioning of this biocatalytic cascade. New theoretical expressions are derived to allow simple, few-parameter modeling of network components concatenated in such cascades, both with and without filtering. The derived expressions are tested against experimental data obtained for the realized network's responses, measured optically, to variations of its input chemicals' concentrations with and without filtering processes. We also describe how the present modeling approach captures and explains several observations and features identified in earlier studies of enzymatic processes when they were considered as potential network components for multi-step information/signal processing systems.

q-bio.MN↗

arXiv2013

Enzymatic AND Logic Gate with Sigmoid Response Induced by Photochemically Controlled Oxidation of the Output

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 gate's 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.

cond-mat.soft↗

arXiv2013

Modularity of Biochemical Filtering for Inducing Sigmoid Response in Both Inputs in an Enzymatic AND Gate

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 gate's 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.

physics.bio-ph↗

arXiv2013

Bioinspired Associative Memory System Based on Enzymatic Cascades

A biomolecular system representing the first realization of associative memory based on enzymatic reactions in vitro has been designed. The system demonstrated "training" and "forgetting" features characteristic of memory in biological systems, but presently realized in simple biocatalytic cascades.

q-bio.MN↗

arXiv2013

Two-Input Enzymatic Logic Gates Made Sigmoid by Modifications of the Biocatalytic Reaction Cascades

Computing based on biochemical processes is a newest rapidly developing field of unconventional information and signal processing. In this paper we present results of our research in the field of biochemical computing and summarize the obtained numerical and experimental data for implementations of the standard two-input OR and AND gates with double-sigmoid shape of the output signal. This form of response was obtained as a function of the two inputs in each of the realized biochemical systems. The enzymatic gate processes in the first system were activated with two chemical inputs and resulted in optically detected chromogen oxidation, which happens when either one or both of the inputs are present. In this case, the biochemical system is functioning as the OR gate. We demonstrate that the addition of a "filtering" biocatalytic process leads to a considerable reduction of the noise transmission factor and the resulting gate response has sigmoid shape in both inputs. The second system was developed for functioning as an AND gate, where the output signal was activated only by a simultaneous action of two enzymatic biomarkers. This response can be used as an indicator of liver damage, but only if both of these of the inputs are present at their elevated, pathophysiological values of concentrations. A kinetic numerical model was developed and used to estimate the range of parameters for which the experimentally realized logic gate is close to optimal. We also analyzed the system to evaluate its noise-handling properties.

physics.bio-ph↗

arXiv2013

Enzyme-Based Logic: OR Gate with Double-Sigmoid Filter Response

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.

q-bio.MN↗

arXiv2013

Realization of Associative Memory in an Enzymatic Process: Towards Biomolecular Networks with Learning and Unlearning Functionalities

We report a realization of an associative memory signal/information processing system based on simple enzyme-catalyzed biochemical reactions. Optically detected chemical output is always obtained in response to the triggering input, but the system can also "learn" by association, to later respond to the second input if it is initially applied in combination with the triggering input as the "training" step. This second chemical input is not self-reinforcing in the present system, which therefore can later "unlearn" to react to the second input if it is applied several times on its own. Such processing steps realized with (bio)chemical kinetics promise applications of bio-inspired/memory-involving components in "networked" (concatenated) biomolecular processes for multi-signal sensing and complex information processing.

q-bio.MN↗

arXiv2013

Enzyme-Based Logic Analysis of Biomarkers at Physiological Concentrations: AND Gate with Double-Sigmoid "Filter" Response

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.

q-bio.MN↗

arXiv2011

Biomolecular Filters for Improved Separation of Output Signals in Enzyme Logic Systems Applied to Biomedical Analysis

Biomolecular logic systems processing biochemical input signals and producing "digital" outputs in the form of YES/NO were developed for analysis of physiological conditions characteristic of liver injury, soft tissue injury and abdominal trauma. Injury biomarkers were used as input signals for activating the logic systems. Their normal physiological concentrations were defined as logic-0 level, while their pathologically elevated concentrations were defined as logic-1 values. Since the input concentrations applied as logic 0 and 1 values were not sufficiently different, the output signals being at low and high values (0, 1 outputs) were separated with a short gap making their discrimination difficult. Coupled enzymatic reactions functioning as a biomolecular signal processing system with a built-in filter property were developed. The filter process involves a partial back-conversion of the optical-output-signal-yielding product, but only at its low concentrations, thus allowing the proper discrimination between 0 and 1 output values.

cond-mat.soft↗

arXiv2011

Realization and Properties of Biochemical-Computing Biocatalytic XOR Gate Based on Enzyme Inhibition by a Substrate

We consider a realization of the XOR logic gate in a process biocatalyzed by an enzyme (here horseradish peroxidase: HRP), the function of which can be inhibited by a substrate (hydrogen peroxide for HRP), when the latter is inputted at large enough concentrations. A model is developed for describing such systems in an approach suitable for evaluation of the analog noise amplification properties of the gate. The obtained data are fitted for gate quality evaluation within the developed model, and we discuss aspects of devising XOR gates for functioning in "biocomputing" systems utilizing biomolecules for information processing.

cond-mat.soft↗

arXiv2011

Towards Biochemical Filter with Sigmoidal Response to pH Changes: Buffered Biocatalytic Signal Transduction

We realize a biochemical filtering process by introducing a buffer in a biocatalytic signal-transduction logic system based on the function of an enzyme, esterase. The input, ethyl butyrate, is converted into butyric acid-the output signal, which in turn is measured by the drop in the pH value. The developed approach offers a versatile "network element" for increasing the complexity of biochemical information processing systems. Evaluation of an optimal regime for quality filtering is accomplished in the framework of a kinetic rate-equation model.

cond-mat.soft↗

arXiv2010

Enzymatic Logic Gates with Noise-Reducing Sigmoid Response

Biochemical computing is an emerging field of unconventional computing that attempts to process information with biomolecules and biological objects using digital logic. In this work we survey filtering in general, in biochemical computing, and summarize the experimental realization of an AND logic gate with sigmoid response in one of the inputs. The logic gate is realized with electrode-immobilized glucose-6-phosphate dehydrogenase enzyme that catalyzes a reaction corresponding to the Boolean AND functions. A kinetic model is also developed and used to evaluate the extent to which the performance of the experimentally realized logic gate is close to optimal.

cond-mat.soft↗

arXiv2010

Biochemical Filter with Sigmoidal Response: Increasing the Complexity of Biomolecular Logic

The first realization of a designed, rather than natural, biochemical filter process is reported and analyzed as a promising network component for increasing the complexity of biomolecular logic systems. Key challenge in biochemical logic research has been achieving scalability for complex network designs. Various logic gates have been realized, but a "toolbox" of analog elements for interconnectivity and signal processing has remained elusive. Filters are important as network elements that allow control of noise in signal transmission and conversion. We report a versatile biochemical filtering mechanism designed to have sigmoidal response in combination with signal-conversion process. Horseradish peroxidase-catalyzed oxidation of chromogenic electron donor by hydrogen peroxide, was altered by adding ascorbate, allowing to selectively suppress the output signal, modifying the response from convex to sigmoidal. A kinetic model was developed for evaluation of the quality of filtering. The results offer improved capabilities for design of scalable biomolecular information processing systems.

physics.bio-ph↗

arXiv2010

Realization and Properties of Biochemical-Computing Biocatalytic XOR Gate Based on Signal Change

We consider a realization of the XOR logic gate in a system involving two competing biocatalytic reactions, for which the logic-1 output is defined by these two processes causing a change in the optically detected signal. A model is developed for describing such systems in an approach suitable for evaluation of the analog noise amplification properties of the gate and optimization of its functioning. The initial data are fitted for gate quality evaluation within the developed model, and then modifications are proposed and experimentally realized for improving the gate functioning.

cond-mat.soft↗