Publications by authors named "Bahador Marzban"

6 Publications

  • Page 1 of 1

Quantitative analysis of mitochondrial ATP synthesis.

Math Biosci 2021 Jun 17:108646. Epub 2021 Jun 17.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, 48109, MI, USA. Electronic address:

We present a computational framework for analyzing and simulating mitochondrial ATP synthesis using basic thermodynamic and kinetic principles. The framework invokes detailed descriptions of the thermodynamic driving forces associated with the processes of the electron transport chain, mitochondrial ATP synthetase, and phosphate and adenine nucleotide transporters. Assembling models of these discrete processes into an integrated model of mitochondrial ATP synthesis, we illustrate how to analyze and simulate in vitro respirometry experiments and how models identified from in vitro experimental data effectively explain cardiac respiratory control in vivo. Computer codes for these analyses are embedded as Python scripts in a Jupyter Book to facilitate easy adoption and modification of the concepts developed here. This accessible framework may also prove useful in supporting educational applications. All source codes are available on at https://beards-lab.github.io/QAMAS_book/.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.mbs.2021.108646DOI Listing
June 2021

Impaired Myocardial Energetics Causes Mechanical Dysfunction in Decompensated Failing Hearts.

Function (Oxf) 2020 22;1(2):zqaa018. Epub 2020 Sep 22.

Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.

Cardiac mechanical function is supported by ATP hydrolysis, which provides the chemical-free energy to drive the molecular processes underlying cardiac pumping. Physiological rates of myocardial ATP consumption require the heart to resynthesize its entire ATP pool several times per minute. In the failing heart, cardiomyocyte metabolic dysfunction leads to a reduction in the capacity for ATP synthesis and associated free energy to drive cellular processes. Yet it remains unclear if and how metabolic/energetic dysfunction that occurs during heart failure affects mechanical function of the heart. We hypothesize that changes in phosphate metabolite concentrations (ATP, ADP, inorganic phosphate) that are associated with decompensation and failure have direct roles in impeding contractile function of the myocardium in heart failure, contributing to the whole-body phenotype. To test this hypothesis, a transverse aortic constriction (TAC) rat model of pressure overload, hypertrophy, and decompensation was used to assess relationships between metrics of whole-organ pump function and myocardial energetic state. A multiscale computational model of cardiac mechanoenergetic coupling was used to identify and quantify the contribution of metabolic dysfunction to observed mechanical dysfunction. Results show an overall reduction in capacity for oxidative ATP synthesis fueled by either fatty acid or carbohydrate substrates as well as a reduction in total levels of adenine nucleotides and creatine in myocardium from TAC animals compared to sham-operated controls. Changes in phosphate metabolite levels in the TAC rats are correlated with impaired mechanical function, consistent with the overall hypothesis. Furthermore, computational analysis of myocardial metabolism and contractile dynamics predicts that increased levels of inorganic phosphate in TAC compared to control animals kinetically impair the myosin ATPase crossbridge cycle in decompensated hypertrophy/heart failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/function/zqaa018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552914PMC
September 2020

Effect of pressure profile of shock waves on lipid membrane deformation.

PLoS One 2019 21;14(2):e0212566. Epub 2019 Feb 21.

Department of Mechanical, Industrial & Systems Engineering, University of Rhode Island, Kingston, RI, United States of America.

Use of shock waves to temporarily increase the permeability of the cell membrane is a promising approach in drug delivery and gene therapy to allow the translocation of macromolecules and small polar molecules into the cytoplasm. Our understanding of how the characteristics of the pressure profile of shock waves, such as peak pressure and pulse duration, influences membrane properties is limited. Here we study the response of lipid bilayer membranes to shock pulses with different pressure profiles using atomistic molecular dynamics simulations. From our simulation results, we find that the transient deformation/disordering of the membrane depends on both the magnitude and the pulse duration of the pressure profile of the shock pulse. For a low pressure impulse, peak pressure has a dominant effect on membrane structural changes, while for the high pressure impulse, we find that there exists an optimal pulse duration at which membrane deformation/disordering is maximized.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212566PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6383940PMC
November 2019

A minimal mechanics model for mechanosensing of substrate rigidity gradient in durotaxis.

Biomech Model Mechanobiol 2018 Jun 22;17(3):915-922. Epub 2018 Jan 22.

Department of Mechanical, Industrial and Systems Engineering, University of Rhode Island, Kingston, RI, 02881, USA.

Durotaxis refers to the phenomenon in which cells can sense the spatial gradient of the substrate rigidity in the process of cell migration. A conceptual two-part theory consisting of the focal adhesion force generation and mechanotransduction has been proposed previously by Lo et al. to explain the mechanism underlying durotaxis. In the present work, we are concerned with the first part of the theory: how exactly is the larger focal adhesion force generated in the part of the cell adhering to the stiffer region of the substrate? Using a simple elasticity model and by assuming the cell adheres to the substrate continuously underneath the whole cell body, we show that the mechanics principle of static equilibrium alone is sufficient to account for the generation of the larger traction stress on the stiffer region of the substrate. We believe that our model presents a simple mechanistic understanding of mechanosensing of substrate stiffness gradient at the cellular scale, which can be incorporated in more sophisticated mechanobiochemical models to address complex problems in mechanobiology and bioengineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10237-018-1001-3DOI Listing
June 2018

Myofibrils in Cardiomyocytes Tend to Assemble Along the Maximal Principle Stress Directions.

J Biomech Eng 2017 Dec;139(12)

Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, School of Engineering and Applied Sciences, Harvard University, Cambridge, MA 02138 e-mail: .

The mechanisms underlying the spatial organization of self-assembled myofibrils in cardiac tissues remain incompletely understood. By modeling cells as elastic solids under active cytoskeletal contraction, we found a good correlation between the predicted maximal principal stress directions and the in vitro myofibril orientations in individual cardiomyocytes. This implies that actomyosin fibers tend to assemble along the maximal tensile stress (MTS) directions. By considering the dynamics of focal adhesion and myofibril formation in the model, we showed that different patterns of myofibril organizations in mature versus immature cardiomyocytes can be explained as the consequence of the different levels of force-dependent remodeling of focal adhesions. Further, we applied the mechanics model to cell pairs and showed that the myofibril organizations can be regulated by a combination of multiple factors including cell shape, cell-substrate adhesions, and cell-cell adhesions. This mechanics model can guide the rational design in cardiac tissue engineering where recapitulating in vivo myofibril organizations is crucial to the contractile function of the heart.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1115/1.4037795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5691293PMC
December 2017

The Effect of Thermal Fluctuation on the Receptor-Mediated Adhesion of a Cell Membrane to an Elastic Substrate.

Membranes (Basel) 2017 Apr 27;7(2). Epub 2017 Apr 27.

Department of Mechanical, Industrial & Systems Engineering, University of Rhode Island, Kingston, RI 02881, USA.

Mechanics of the bilayer membrane play an important role in many biological and bioengineering problems such as cell-substrate and cell-nanomaterial interactions. In this work, we study the effect of thermal fluctuation and the substrate elasticity on the cell membrane-substrate adhesion. We model the adhesion of a fluctuating membrane on an elastic substrate as a two-step reaction comprised of the out-of-plane membrane fluctuation and the receptor-ligand binding. The equilibrium closed bond ratio as a function of substrate rigidity was computed by developing a coupled Fourier space Brownian dynamics and Monte Carlo method. The simulation results show that there exists a crossover value of the substrate rigidity at which the closed bond ratio is maximal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/membranes7020024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489858PMC
April 2017
-->