Sergii Domanskyi

Percolation modeling of self-damaging of composite materials

We propose the concept of autonomous self-damaging in “smart” composite materials, controlled by activation of added nanosize “damaging” capsules. Percolation-type modeling approach earlier applied to the related concept of self-healing materials, is used to investigate the behavior of the initial material’s fatigue. We aim at achieving a relatively sharp drop in the material’s integrity after some initial limited fatigue develops in the course of the sample’s usage. Our theoretical study considers a two-dimensional lattice model and involves Monte Carlo simulations of the connectivity and conductance in the high-connectivity regime of percolation. We give several examples of local capsule–lattice and capsule–capsule activation rules and show that the desired self-damaging property can only be obtained with rather sophisticated “smart” material’s response involving not just damaging but also healing capsules.

Glucose-Triggered Insulin Release from Fe3+-Cross-linked Alginate Hydrogel: Experimental Study and Theoretical Modeling

We study the mechanisms involved in the release, triggered by the application of glucose, of insulin entrapped in Fe3+ -cross-linked alginate hydrogel particles further stabilized with a polyelectrolyte. Platelet-shaped alginate particles are synthesized containing enzyme glucose oxidase conjugated with silica nanoparticles, which are also entrapped in the hydrogel. Glucose diffuses in from solution, and production of hydrogen peroxide is catalyzed by the enzyme within the hydrogel. We argue that, specifically for the Fe3+ -cross-linked systems, the produced hydrogen peroxide is further converted to free radicals via a Fenton-type reaction catalyzed by the iron cations. The activity of free radicals, as well as the reduction of Fe3+ by the enzyme, and other mechanisms contribute to the decrease in density of the hydrogel. As a result, while the particles remain intact, void sizes increase and release of insulin ensues and is followed experimentally. A theoretical description of the involved processes is proposed and utilized to fit the data. It is then used to study the long-time properties of the release process that offers a model for designing new drug-release systems.

Diffusion of Oligonucleotides from within Iron‐Cross‐Linked, Polyelectrolyte‐Modified Alginate Beads: A Model System for Drug Release

An analytical model to describe diffusion of oligonucleotides from stable hydrogel beads is developed and experimentally verified. The synthesized alginate beads are Fe(3+) -cross-linked and 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, that is, the absence of a surface-layer barrier in this case. Furthermore, the results suggest a new simple approach to measuring the diffusion coefficient of mobile oligonucleotide molecules inside hydrogels. 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, which induces full oligonucleotide release with nondiffusional kinetics.

Modeling and Modifying Response of Biochemical Processes for Biocomputing and Biosensing Signal Processing

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 system’s 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.

Experimental Realization of a High-Quality Biochemical XOR Gate

We report an experimental realization of a biochemical XOR gate function that avoids many of the pitfalls of earlier realizations based on biocatalytic cascades. Inputs-represented by pairs of chemicals-cross-react to largely cancel out when both are nearly equal. The cross-reaction can be designed to also optimize gate functioning for noise handling. When not equal, the residual inputs are further processed to result in the output of the XOR type, by biocatalytic steps that allow for further gate-function optimization. The quality of the realized XOR gate is theoretically analyzed.

Design of High Quality Chemical XOR Gates with Noise Reduction

We describe a chemical XOR gate design that realizes gate-response function with filtering properties. Such gate-response function is flat (has small gradients) at and in the vicinity of all the four binary-input logic points, resulting in analog noise suppression. The gate functioning involves cross-reaction of the inputs represented by pairs of chemicals to produce a practically zero output when both are present and nearly equal. This cross-reaction processing step is also designed to result in filtering at low output intensities by canceling out the inputs if one of the latter has low intensity compared with the other. The remaining inputs, which were not reacted away, are processed to produce the output XOR signal by chemical steps that result in filtering at large output signal intensities. We analyze the tradeoff resulting from filtering, which involves loss of signal intensity. We also discuss practical aspects of realizations of such XOR gates.

SIRT6 knockout cells resist apoptosis initiation but not progression: a computational method to evaluate the progression of apoptosis

Apoptosis is essential for numerous processes, such as development, resistance to infections, and suppression of tumorigenesis. Here, we investigate the influence of the nutrient sensing and longevity-assuring enzyme SIRT6 on the dynamics of apoptosis triggered by serum starvation. Specifically, we characterize the progression of apoptosis in wild type and SIRT6 deficient mouse embryonic fibroblasts using time-lapse flow cytometry and computational modelling based on rate-equations and cell distribution analysis. We find that SIRT6 deficient cells resist apoptosis by delaying its initiation. Interestingly, once apoptosis is initiated, the rate of its progression is higher in SIRT6 null cells compared to identically cultured wild type cells. However, SIRT6 null cells succumb to apoptosis more slowly, not only in response to nutrient deprivation but also in response to other stresses. Our data suggest that SIRT6 plays a role in several distinct steps of apoptosis. Overall, we demonstrate the utility of our computational model to describe stages of apoptosis progression and the integrity of the cellular membrane. Such measurements will be useful in a broad range of biological applications.