Browsing by Author "Makarov, Vladimir I."
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- Computational modeling of In vitro swelling of mitochondria: A biophysical approachPublication . Makarov, Vladimir I.; Khmelinskii, Igor; Javadov, SabzaliSwelling of mitochondria plays an important role in the pathogenesis of human diseases by stimulating mitochondria-mediated cell death through apoptosis, necrosis, and autophagy. Changes in the permeability of the inner mitochondrial membrane (IMM) of ions and other substances induce an increase in the colloid osmotic pressure, leading to matrix swelling. Modeling of mitochondrial swelling is important for simulation and prediction of in vivo events in the cell during oxidative and energy stress. In the present study, we developed a computational model that describes the mechanism of mitochondrial swelling based on osmosis, the rigidity of the IMM, and dynamics of ionic/neutral species. The model describes a new biophysical approach to swelling dynamics, where osmotic pressure created in the matrix is compensated for by the rigidity of the IMM, i.e., osmotic pressure induces membrane deformation, which compensates for the osmotic pressure effect. Thus, the effect is linear and reversible at small membrane deformations, allowing the membrane to restore its normal form. On the other hand, the membrane rigidity drops to zero at large deformations, and the swelling becomes irreversible. As a result, an increased number of dysfunctional mitochondria can activate mitophagy and initiate cell death. Numerical modeling analysis produced results that reasonably describe the experimental data reported earlier.
- Contrary to consensus, oxidation of ethanol by human alcohol dehydrogenase (ADH) 1A is activated by ATPPublication . Khmelinskii, Igor; Makarov, Vladimir I.Presently we report that enzymatic oxidation of ethanol (EtOH) by ADH1A alcohol dehydrogenase is strongly accelerated in presence of adenosine triphosphate (ATP), by up to the factor of 20 in vitro. This result provides a different look on the role of ATP in functioning of alcohol dehydrogenases (ADH), which until presently were a textbook example of enzymes not requiring ATP and successfully operating without it. However, ATP is available in every living cell and will activate reactions conducted by ADH enzymes in vivo. Therefore, the body of published literature describing properties of numerous ADH enzymes requires a thorough revision.
- Effects of pulsed electric fields on exciton propagation efficiency along Müller cell intermediate filaments. Possible separation mechanism of high- and low-contrast images by the eye-brain systemPublication . Khmelinskii, Igor; Makarov, Vladimir I.In the current study, we tested a possible mechanism of low-and high-contrast image component discrimination by the vertebrate eye-brain system. Apparently the eye-brain system has to discriminate between the low-contrast image component formed by light scattered within the retina, due to interaction of photons with cells and their parts, and the high-contrast image component transmitted by excitons via the quantum mechanism. Presently, effects of pulsed electric fields applied to Muller cell (MC) intermediate filaments (IFs) on the efficiency of exciton propagation were explored. The effects of both pulse duration and amplitude were recorded. These experimental results show that the eye-brain system may be using signal modulation to discriminate between high-and low-contrast image components, improving our understanding of high-contrast vision in vertebrates.
- Energy transfer along Müller cell intermediate filaments isolated from porcine retina: II. Excitons at 2500 cm−1 produced by ADH1A upon hydrolysis of one ATP moleculePublication . Khmelinskii, Igor; Makarov, Vladimir I.Low-energy (IR -2500 cm-1) exciton transfer was explored in Muller cell (MC) intermediate filaments (IFs) isolated from porcine retina and filling a capillary matrix. IR excitons were generated either by absorption of IR radiation at 4 mu m, or by ATP hydrolysis energy transfer to the MC IFs. ATP hydrolysis was catalyzed by human alcohol dehydrogenase (ADH1A) in ADH1A...NAD+...IF complexes. Each exciton was generated by hydrolysis of one ATP molecule. Exciton energy was independent on ATP concentration. The emission spectra of IR excitons arriving to the other side of the capillary matrix were dependent on the exciton generation method. Timeresolved experiments with direct exciton generation by pulsed IR radiation allowed to measure exciton travel velocity, along with the exciton emission time. The results obtained support new ideas on ATP energy transfer along protein filaments in vivo. These unique experimental results provide for detailed understanding of the electronic state structure of the MC IFs. This study reports that MC IFs isolated from porcine retina have a longliving low-lying electronic excited state at 2500 cm-1 above the ground state.
- External control of the Drosophila melanogaster egg to imago development period by specific combinations of 3D low-frequency electric and magnetic fieldsPublication . Makarov, Vladimir I.; Khmelinskii, IgorWe report that the duration of the egg-to-imago development period of the Drosophila melanogaster, and the imago longevity, are both controllable by combinations of external 3-dimensional (3D) low-frequency electric and magnetic fields (LFEMFs). Both these periods may be reduced or increased by applying an appropriate configuration of external 3D LFEMFs. We report that the longevity of D. melanogaster imagoes correlates with the duration of the egg-to-imago development period of the respective eggs. We infer that metabolic processes in both eggs and imago are either accelerated (resulting in reduced time periods) or slowed down (resulting in increased time periods). We propose that external 3D LFEMFs induce electric currents in live systems as well as mechanical vibrations on sub-cell, whole-cell and cell-group levels. These external fields induce media polarization due to ionic motion and orientation of electric dipoles that could moderate the observed effects. We found that the longevity of D. melanogaster imagoes is affected by action of 3D LFEMFs on the respective eggs in the embryonic development period (EDP). We interpret this effect as resulting from changes in the regulation mechanism of metabolic processes in D. melanogaster eggs, inherited by the resulting imagoes. We also tested separate effects of either 3D electric or 3D magnetic fields, which were significantly weaker.
- In silico simulation of reversible and irreversible swelling of mitochondria: The role of membrane rigidityPublication . Makarov, Vladimir I.; Khmelinskii, Igor; Khuchua, Zaza; Javadov, SabzaliMitochondria have been widely accepted as the main source of ATP in the cell. The inner mitochondrial membrane (IMM) is important for the maintenance of ATP production and other functions of mitochondria. The electron transport chain (ETC) generates an electrochemical gradient of protons known as the proton-motive force across the IMM and thus produces the mitochondrial membrane potential that is critical to ATP synthesis. One of the main factors regulating the structural and functional integrity of the IMM is the changes in the matrix volume. Mild (reversible) swelling regulates mitochondrial metabolism and function; however, excessive (irreversible) swelling causes mitochondrial dysfunction and cell death. The central mechanism of mitochondrial swelling includes the opening of non-selective channels known as permeability transition pores (PTPs) in the IMM by high mitochondrial Ca2+ and reactive oxygen species (ROS). The mechanisms of reversible and irreversible mitochondrial swelling and transition between these two states are still unknown. The present study elucidates an upgraded biophysical model of reversible and irreversible mitochondrial swelling dynamics. The model provides a description of the PTP regulation dynamics using an additional differential equation. The rigidity tensor was used in numerical simulations of the mitochondrial parameter dynamics with different initial conditions defined by Ca2+ concentration in the sarco/endoplasmic reticulum. We were able to estimate the values of the IMM rigidity tensor components by fitting the model to the previously reported experimental data. Overall, the model provides a better description of the reversible and irreversible mitochondrial swelling dynamics.
- IR exciton activation mechanism of ethanol oxidation by human alcohol dehydrogenase (ADH) 1A enzymePublication . Khmelinskii, Igor; Makarov, Vladimir I.Low-energy (2500 cm(-1)) exciton transfer was explored in Muller cell (MC) intermediate filaments (IFs) isolated from porcine retina and filling a capillary matrix. Excitons were generated by absorption of IR radiation at 4 mu m. The effects of these excitons on ethanol oxidation by human alcohol dehydrogenase (ADH1A) enzyme were quantified. It was found that IR excitons transferred to the enzyme accelerated alcohol oxidation rate, which increased by the factor of 2.76 when exciting the IFs with 2.39 mu W/cm(2) of 4 mu m IR light. Power dependence of the oxidation rate was also explored. These results show that IFs may be transmitting energy to enzyme mole-cules in vivo, facilitating enzymatic reactions. The required excitons may be produced by cells at the cost of adenosine triphosphate (ATP) hydrolysis energy. Therefore, such control mechanism for enzymatic reactions may be operational in living systems. Direct activation of the enzyme by IR radiation with 4 mu m wavelength did not occur; instead, indirect activation of the IF...ADH1A...NAD (nicotinamide adenine dinucleotide)...EtOH complex occurred by energy transfer of the IR exciton to the ADH1A molecule of this complex. Considering that every living cell has a network of IFs, a similar reaction control mechanism may be operational in vivo, providing a much faster energy supply redirection within the cell than ATP diffusion, and justifying a closer inquiry.
- Macroscopic excitation energy transport in a structured Co nanolayerPublication . Khmelinskii, Igor; Makarov, Vladimir I.We report absorption spectra of the 7.3-and 11.3-nm Co nanolayers and emission of a structured Co nanolayer. The structure contains a 7.3-nm Co nanolayer covering a 25 x 25 mm(2) fused silica substrate, with a thicker 11.3-nm Co track in the middle of the substrate. We report that the radiation energy absorbed by the entire Co nanolayer is transferred to the thicker nanotrack. The transferred energy is reemitted by the track, with the emission spectra containing well-defined emission bands, strongly dependent on the excitation wavelength. We report that the bands appearing in the emission spectra of the nanotrack correspond to the transitions from the higher electronic excited states of the nanotrack to its first excited state. We therefore identify the observed emission as the superemission of the Co nanotrack. The superemission quantum yield is dependent on the excitation wavelength, decreasing at higher excitation energies. We propose a theoretical model that explains the results obtained. The model analysis produced estimates of several model parameters.
- Mitochondrial ATP synthesis activated by exciton energy transfer from Müller cell intermediate filamentsPublication . Khmelinskii, Igor; Makarov, Vladimir I.ATP production by mitochondria isolated from yeast cells (S. cerevisiae) was accelerated by exciton energy transfer from intermediate filaments (IFs). The effect was dependent on mitochondrial concentration and the intensity of light used to generate excitons. Presumably, mitochondrial cytochrome C (CC) was activated by IF exciton energy transfer to CC in the inner mitochondrial membrane (IMM), generating electronically excited CC, and the respective excitation energy was then used in the ATP production chain. A qualitative model was proposed describing observations, although more experiments are required before the detailed mechanisms could be deduced. The present results support the earlier proposed hypothesis of ATP production in vertebrate retina by excess photons in daytime, when retina needs extra energy for recovering the used opsins. Additionally, it shows that at early stages of evolution mitochondria could have been using solar radiation to produce ATP.
- Optical properties of ZnO semiconductor nanolayersPublication . Khmelinskii, Igor; Makarov, Vladimir I.Presently we explore absorption and emission spectra of ZnO semiconductor nanolayers 4.1-17.3 nm thick. We report that their absorption spectra have discrete structure, with the transition band density increasing with the nanolayer thickness. The emission spectra recorded at 4.1 and 9.3 nm thickness have resolved band structure, with the bands partially overlapping in the 9.3 nm sample. On the other hand, the emission spectra are strongly overlapped in the 13.1 and 17.3 nm samples. We used our modeling approach that considers electronic states in a one-dimensional infinite potential well, calculating the relative electron mass of 0.205, and the starting quantum number for the absorption transitions of 7, 8, 9 and 9, for the respective samples. We also discuss the present results using the traditional approach of solid-state physics, considering potential surfaces in the linear momentum space.