Vahid Rezania

Publications of Vahid Rezania

• A Physiologically-Based Flow Network Model for Hepatic Drug Elimination I: Regular Lattice Lobule Model

  Authors: Vahid Rezania, Rebeccah E Marsh, Dennis Coombe, Jack A Tuszynski

  11/2011;

  We develop a physiologically-based lattice model for the transport and metabolism of drugs in the functional unit of the liver, called the lobule. In contrast to earlier studies, we have emphasizedWe develop a physiologically-based lattice model for the transport and metabolism of drugs in the functional unit of the liver, called the lobule. In contrast to earlier studies, we have emphasized the dominant role of convection in well-vascularized tissue with a given structure. Estimates of convective, diffusive and reaction contributions are given. We have compared drug concentration levels observed exiting the lobule with their predicted detailed distribution inside the lobule, assuming that most often the former is accessible information while the latter is not.

• Modeling the effects of drug binding on the dynamic instability of microtubules.

  Authors: Peter Hinow, Vahid Rezania, Manu Lopus, Mary Ann Jordan, Jack A Tuszyński

  Physical biology. 08/2011; 8(5):056004.

  We propose a stochastic model that accounts for the growth, catastrophe and rescue processes of steady-state microtubules assembled from MAP-free tubulin in the possible presence of aWe propose a stochastic model that accounts for the growth, catastrophe and rescue processes of steady-state microtubules assembled from MAP-free tubulin in the possible presence of a microtubule-associated drug. As an example of the latter, we both experimentally and theoretically study the perturbation of microtubule dynamic instability by S-methyl-D-DM1, a synthetic derivative of the microtubule-targeted agent maytansine and a potential anticancer agent. Our model predicts that among the drugs that act locally at the microtubule tip, primary inhibition of the loss of GDP tubulin results in stronger damping of microtubule dynamics than inhibition of GTP tubulin addition. On the other hand, drugs whose action occurs in the interior of the microtubule need to be present in much higher concentrations to have visible effects.

• Model of ionic currents through microtubule nanopores and the lumen.

  Authors: Holly Freedman, Vahid Rezania, Avner Priel, Eric Carpenter, Sergei Y Noskov, Jack A Tuszynski

  Physical review. E, Statistical, nonlinear, and soft matter physics. 05/2010; 81(5 Pt 1):051912.

  It has been suggested that microtubules and other cytoskeletal filaments may act as electrical transmission lines. An electrical circuit model of the microtubule is constructed incorporating featuresIt has been suggested that microtubules and other cytoskeletal filaments may act as electrical transmission lines. An electrical circuit model of the microtubule is constructed incorporating features of its cylindrical structure with nanopores in its walls. This model is used to study how ionic conductance along the lumen is affected by flux through the nanopores, both with and without an external potential applied across its two ends. Based on the results of Brownian dynamics simulations, the nanopores were found to have asymmetric inner and outer conductances, manifested as nonlinear IV curves. Our simulations indicate that a combination of this asymmetry and an internal voltage source arising from the motion of the C-terminal tails causes cations to be pumped across the microtubule wall and propagate in both directions down the microtubule through the lumen, returning to the bulk solution through its open ends. This effect is demonstrated to add directly to the longitudinal current through the lumen resulting from an external voltage source applied across the two ends of the microtubule. The predicted persistent currents directed through the microtubule wall and along the lumen could be significant in directing the dissipation of weak, endogenous potential gradients toward one end of the microtubule within the cellular environment.

• Continuous model for microtubule dynamics with catastrophe, rescue, and nucleation processes.

  Authors: Peter Hinow, Vahid Rezania, Jack A Tuszyński

  Physical review. E, Statistical, nonlinear, and soft matter physics. 09/2009; 80(3 Pt 1):031904.

  Microtubules are a major component of the cytoskeleton distinguished by highly dynamic behavior both in vitro and in vivo referred to as dynamic instability. We propose a general mathematical modelMicrotubules are a major component of the cytoskeleton distinguished by highly dynamic behavior both in vitro and in vivo referred to as dynamic instability. We propose a general mathematical model that accounts for the growth, catastrophe, rescue, and nucleation processes in the polymerization of microtubules from tubulin dimers. Our model is an extension of various mathematical models developed earlier formulated in order to capture and unify the various aspects of tubulin polymerization. While attempting to use a minimal number of adjustable parameters, the proposed model covers a broad range of behaviors and has predictive features discussed in the paper. We have analyzed the range of resultant dynamical behavior of the microtubules by changing each of the parameter values at a time and observing the emergence of various dynamical regimes that agree well with the previously reported experimental data and behavior.

• Microtubule Assembly of Isotypically Purified Tubulin and Its Mixtures.

  Authors: Vahid Rezania, Olga Azarenko, Mary Ann Jordan, Hannes Bolterauer, Richard F Ludueña, J Torin Huzil, Jack A Tuszynski

  Biophysical journal. 06/2008;

  Numerous isotypes of the structural protein tubulin have now been characterized in various organisms and their expression offers a plausible explanation for observed differences affecting microtubuleNumerous isotypes of the structural protein tubulin have now been characterized in various organisms and their expression offers a plausible explanation for observed differences affecting microtubule function in vivo. While this is an attractive hypothesis, there are only a handful of studies demonstrating a direct influence of tubulin isotype composition on the dynamic properties of microtubules. Here, we present the results of experimental assays on the assembly of microtubules from bovine brain tubulin using purified isotypes at various controlled relative concentrations. A novel data analysis is developed using recursive maps which are shown to be related to the master equation formalism. We have found striking similarities between the three isotypes of bovine tubulin studied in regard to their dynamic instability properties, except for subtle differences in their catastrophe frequencies. When mixtures of tubulin isotypes are analyzed, their nonlinear concentration dependence is modeled and interpreted in terms of lower affinities of tubulin dimers belonging to the same isotype than those that represent different isotypes indicating hitherto unsuspected influences of tubulin dimers on each other within a microtubule. Finally, we investigate the fluctuations in microtubule assembly and disassembly rates and conclude that the inherent rate variability may signify differences in the GTP composition of the growing and shortening microtubule tips. It is the main objective of this paper to develop a quantitative model of tubulin polymerization for individual isotypes and their mixtures. The possible biological significance of the observed differences is addressed.

• A first principle (3+1)-dimensional model for microtubule polymerization

  Authors: Vahid Rezania, Jack A. Tuszynski

  Physics Letters A.

  In this Letter we propose a microscopic model to study the polymerization of microtubules (MTs). Starting from fundamental reactions during MT's assembly and disassembly processes, we systematicallyIn this Letter we propose a microscopic model to study the polymerization of microtubules (MTs). Starting from fundamental reactions during MT's assembly and disassembly processes, we systematically derive a nonlinear system of equations that determines the dynamics of microtubules in 3D. We found that the dynamics of an MT is mathematically expressed via a cubic–quintic nonlinear Schrödinger (NLS) equation. Interestingly, the generic 3D solution of the NLS equation exhibits linear growing and shortening in time as well as temporal fluctuations about a mean value which are qualitatively similar to the dynamic instability of MTs observed experimentally. By solving equations numerically, we have found spatio-temporal patterns consistent with experimental observations.