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Biomedical subjects

J A Tuszyński

Publications and source records attributed to J A Tuszyński.

17 recordsLinked to original sources
PubMed2006

Application of a random network with a variable geometry of links to the kinetics of drug elimination in healthy and diseased livers.

This paper discusses an application of a random network with a variable number of links and traps to the elimination of drug molecules from the body by the liver. The nodes and links represent the transport vessels, and the traps represent liver cells with metabolic enzymes that eliminate drug molecules. By varying the number and configuration of links and nodes, different disease states of the liver related to vascular damage have been simulated, and the effects on the rate of elimination of a drug have been investigated. Results of numerical simulations show the prevalence of exponential decay curves with rates that depend on the concentration of links. In the case of fractal lattices at the percolation threshold, we find that the decay of the concentration is described by exponential functions for high trap concentrations but transitions to stretched exponential behavior at low trap concentrations.

Animals↗
PubMed2005

Asymptotic time dependence in the fractal pharmacokinetics of a two-compartment model.

We further investigate, both analytically and numerically, the properties of the fractal two-compartment model introduced by Fuite [J. Fuite, R. Marsh, and J. Tuszynski, Phys. Rev. E 66, 021904 (2002)]. Specifically, we look at the effects of the fractal exponent of the elimination rate coefficient on the long-time behavior of the pharmacokinetic clearance tail. For small exponent values, the tail exhibits exponential behavior, while for larger values, there is a transition to a power law. The theory is applied to seven data sets simulating drugs taken from the pharmacological literature.

Computer Simulation↗
PubMed2005

Elastic vibrations in seamless microtubules.

Parameters characterizing elastic properties of microtubules, measured in several recent experiments, reflect an anisotropic character. We describe the microscopic dynamical properties of microtubules using a discrete model based on an appropriate lattice of dimers. Adopting a harmonic approximation for the dimer-dimer interactions and estimating the lattice elastic constants, we make predictions regarding vibration dispersion relations and vibration propagation velocities. Vibration frequencies and velocities are expressed as functions of the elastic constants and of the geometrical characteristics of the microtubules. We show that vibrations which propagate along the protofilament do so significantly faster than those along the helix.

Anisotropy↗
PubMed2005

Anisotropic elastic properties of microtubules.

We review and model the experimental parameters which characterize elastic properties of microtubules. Three macroscopic estimates are made of the anisotropic elastic moduli, accounting for the molecular forces between tubulin dimers: for a longitudinal compression of a microtubule, for a lateral force and for a shearing force. These estimates reflect the anisotropies in these parameters observed in several recent experiments.

Animals↗
PubMed2004

Ionic wave propagation along actin filaments.

We investigate the conditions enabling actin filaments to act as electrical transmission lines for ion flows along their lengths. We propose a model in which each actin monomer is an electric element with a capacitive, inductive, and resistive property due to the molecular structure of the actin filament and viscosity of the solution. Based on Kirchhoff's laws taken in the continuum limit, a nonlinear partial differential equation is derived for the propagation of ionic waves. We solve this equation in two different regimes. In the first, the maximum propagation velocity wave is found in terms of Jacobi elliptic functions. In the general case, we analyze the equation in terms of Fisher-Kolmogoroff modes with both localized and extended wave characteristics. We propose a new signaling mechanism in the cell, especially in neurons.

Actin Cytoskeleton↗
PubMed2003

Non-Gaussian statistics of the vibrational fluctuations of myoglobin.

Experiments on the dynamics of vibrational fluctuations in myoglobin revealed an interesting behavioral cross-over occurring in the range 180-200 K. In this temperature range the mean square displacement of atomic positions versus temperature sharply increases its slope, indicating the dissociation of CO from the heme group. In this paper we develop a theoretical model that provides a framework for the quantitative description of this phenomenon. The basis of our calculations is an assumption of an effective potential with multiple local minima. In particular, we consider a quartic potential in place of the simple quadratic. We then use non-Gaussian statistics to obtain a relationship between the mean square displacement and model parameters. We compare our model to published experimental data and show that it can describe the data set using physically meaningful parameters which are fitted to the experimental data. In the process we verify the Gaussian approximation's applicability only to the low-temperature régime. In the high-temperature limit, however, deviations from the Gaussian approximation are due to the double-well nature of our effective potential. We find that the published datasets showing the thermal transition display the qualitative trends predicted by appropriate algebraic approximations to our predicted myoglobin behavior.

Computer Simulation↗
PubMed2003

Random walks with non-Gaussian step-size distributions and the folding of random polymer chains.

In this paper, we study a random walker whose step-size distribution is of non-Gaussian bimodal form due to the addition of a quartic term in the exponential. By the central limit theorem, we know that in the limit of a large number of steps, the probability distribution representing the distance the walker has traveled becomes Gaussian. We investigate the nature of this convergence both numerically and analytically. We obtain a scaling relation describing the number of steps required for convergence in terms of the width and separation of the peaks of the step-size distribution. We assume in the concluding section that our model is well suited for the application of the folding of a random polymer chain.

Journal Article↗
PubMed2003

Relationship between the nonlinear ferroelectric and liquid crystal models for microtubules.

Microtubules (MTs), which are the main components of the cytoskeleton, are important in a variety of cellular activities, but some physical properties underlying the most important features of their behavior are still lacking satisfactory explanation. One of the essential enigmas regarding the energy balance in MTs is the hydrolysis of the exchangeable guanosine 5'-triphosphate bound to the beta monomer of the molecule. The energy released in the hydrolysis process amounts to 6.25 x 10(-20) J and has been the subject of many attempts to answer the questions of its utilization. Earlier, we put forward a hypothesis that this energy can cause a local conformational distortion of the dimer. This distortion should have nonlinear character and could lead to the formation of a traveling kink soliton. In this paper we use the formalism of the liquid crystal theory to consider the nonlinear dynamics of MTs. We demonstrate that this new model is formally equivalent to our earlier ferroelectric model which was widely exploited in an attempt to elucidate some important dynamical activities in MTs. We also study the stability of kink solitons against small perturbations and their unusual mutual interactions as well as the interactions with structural inhomogeneities of MTs. Our new approach based on liquid crystal properties of microtubules has been recently corroborated by new insights gained from the electrostatic properties of tubulin and microtubules.

Animals↗
PubMed2002

Quantum computation in brain microtubules: decoherence and biological feasibility.

The Penrose-Hameroff orchestrated objective reduction (orch. OR) model assigns a cognitive role to quantum computations in microtubules within the neurons of the brain. Despite an apparently "warm, wet, and noisy" intracellular milieu, the proposal suggests that microtubules avoid environmental decoherence long enough to reach threshold for "self-collapse" (objective reduction) by a quantum gravity mechanism put forth by Penrose. The model has been criticized as regards the issue of environmental decoherence, and a recent report by Tegmark finds that microtubules can maintain quantum coherence for only 10(-13) s, far too short to be neurophysiologically relevant. Here, we critically examine the decoherence mechanisms likely to dominate in a biological setting and find that (1) Tegmark's commentary is not aimed at an existing model in the literature but rather at a hybrid that replaces the superposed protein conformations of the orch. OR theory with a soliton in superposition along the microtubule; (2) recalculation after correcting for differences between the model on which Tegmark bases his calculations and the orch. OR model (superposition separation, charge vs dipole, dielectric constant) lengthens the decoherence time to 10(-5)-10(-4) s; (3) decoherence times on this order invalidate the assumptions of the derivation and determine the approximation regime considered by Tegmark to be inappropriate to the orch. OR superposition; (4) Tegmark's formulation yields decoherence times that increase with temperature contrary to well-established physical intuitions and the observed behavior of quantum coherent states; (5) incoherent metabolic energy supplied to the collective dynamics ordering water in the vicinity of microtubules at a rate exceeding that of decoherence can counter decoherence effects (in the same way that lasers avoid decoherence at room temperature); (6) microtubules are surrounded by a Debye layer of counterions, which can screen thermal fluctuations, and by an actin gel that might enhance the ordering of water in bundles of microtubules, further increasing the decoherence-free zone by an order of magnitude and, if the dependence on the distance between environmental ion and superposed state is accurately reflected in Tegmark's calculation, extending decoherence times by three orders of magnitude; (7) topological quantum computation in microtubules may be error correcting, resistant to decoherence; and (8) the decohering effect of radiative scatterers on microtubule quantum states is negligible. These considerations bring microtubule decoherence into a regime in which quantum gravity could interact with neurophysiology.

Actins↗
PubMed2002

Impact of regulatory proteins on the nonlinear dynamics of DNA.

In this paper we examine the nonlinear dynamics of a DNA chain whose exciton modes are affected by regulatory proteins that may become bound to the DNA chain by hydrogen bonds. The dynamics of the DNA chain is described by the Peyrard-Bishop model. Since this model gives rise to large-amplitude broad oscillations of base pairs, we consider the impact of attached regulatory proteins on the so-called breathers or bubbles. Assuming that an ideal gas of bubbles may exist in the DNA chain at physiological temperatures we adopt a statistical approach to calculate the average size of base-pair stretching under the prevailing conditions.

Adenine↗
PubMed2001

Quantitative analysis of the frequency spectrum of the radiation emitted by cytochrome oxidase enzymes.

A physical model is proposed that provides a quantitative analysis of the energy emitted by proton flows through mitochondrial walls. The model developed is based on biochemical and biophysical properties of the enzyme cytochrome oxidase and in particular the embedded heme groups that are involved in the electron ferrying mechanism. The estimates of the energies at approximately 1.1 eV and corresponding wavelengths of the near infrared radiation generated, with a peak close to 900 nm, agree extremely well with experimental values. The basic idea in the mechanism proposed is that the passage of a proton through the mitochondrial wall's gate is linked with the creation of a virtual proton-electron pair in an excited state of a hydrogen atom. The electron is temporarily removed from the enzyme when the proton arrives at the gate and is subsequently deposited back at the enzyme's acceptor site when the proton leaves the gate.

Biophysical Phenomena↗
PubMed1999

Microtubules: strange polymers inside the cell.

This paper provides a consistent approach (within a one-dimensional approximation) to the description of the evolution of the microtubule length at both low- and high-density concentrations. We derive general master-type equations which are based on the key chemical reactions involved in the assembly and disassembly of microtubules. The processes included are: polymerization and depolymerization of a single protein dimer, catastrophic disassembly affecting an a piori arbitrary number of dimers, and a rescue event. Solutions of the derived equations are compared with the existing experimental data. Important conclusions linking the emergence of bell-shaped histograms with the nature of catastrophe and rescue phenomena are drawn. Finally, we briefly discuss the emergence of coherent phenomena in microtubule polymerization, i.e., a transition to collective oscillations in the assembly and disassembly effects.

Biopolymers↗
PubMed1999

DNA dynamics and endogeneous fields.

In this paper we investigate the influence of endogeneous AC fields, generated by a living cell itself, on DNA dynamics. Both quantum nonlinear vibron-phonon interaction model and a model of a highly localized excitation are used. The transition of a broad solitonic excitation into a highly localized one affected by AC fields is calculated using Kubo's formalism for linear response of the system.

DNA↗
PubMed1997

Selected physical issues in the structure and function of microtubules.

The cytoskeleton consists of networks of protein polymers which structurally and dynamically organize interiors of living cells. Microtubules exhibit a complex array of self-organization phenomena which are very sensitive to various laboratory conditions. In this paper we discuss the main features of microtubules focusing our attention on a selection of their physical properties, i.e., the questions of assembly dynamics and energy transfer along their protofilaments, the possible dipolar phases which we predict to exist, and, finally, the hypothesis of current flows associated with the electric field lines produced by cytoskeletal components.

Animals↗
PubMed1997

The enigma of microtubules and their self-organizing behavior in the cytoskeleton.

The cytoskeleton of eukaryotic cells contains networks of protein polymers called microtubules which structurally and functionally organize their interiors. Both in vivo and in vitro microtubules exhibit a fascinating and yet poorly understood array of important functions involving complex self-organization phenomena which are very sensitive to physiological and laboratory conditions, respectively. In this paper we discuss the main physical characteristics of microtubules focusing our attention on four particular aspects: (a) the dynamics of their assembly and disassembly processes (b) the types and the range of existence of ordered dipolar phases and (c) modes of energy transfer and (d) information processing capabilities.

Animals↗
PubMed1983

Theory of long-range coherence in biological systems. I. The anomalous behaviour of human erythrocytes.

In this paper, an explicit expression of the interaction potential has been obtained, based on the Fröhlich model of long-range coherence in biological cells. These theoretical expressions are used to correlate with the experimental data obtained from the light scattering and the Brownian motion for the red blood cells (human erythrocytes). The necessary conditions are derived for the formation of rouleaux in human erythrocytes in the presence of long range interactions. The kinetics of rouleaux formation in terms of the properties of the diffusion coefficient has been investigated. It is concluded that both types of experimental data can be interpreted satisfactorily by this model.

Cell Movement↗