Meitham Amereh

Unveiling the role of metabolic rates variation in driving tumor heterogeneity and controlling growth and invasion: insights from an integrated multiscale in-vitro in-silico framework

The three-dimensional (3D) structure of solid tumors inherently limits oxygen and nutrient diffus... more The three-dimensional (3D) structure of solid tumors inherently limits oxygen and nutrient diffusion to deeper cells, resulting in morphological and metabolic variations. Non-physiological levels of oxygen and nutrients within the tumors result in heterogeneous cell populations that exhibit distinct necrotic, hypoxic, and proliferative zones. Among these zonal cellular properties, metabolic rates strongly affect the overall growth and invasion of tumors. Here we report on a hybrid discrete-continuum (HDC) mathematical framework that uses data from a biomimetic three-dimensional (3D) in vitro cancer model to accurately predict cancer growth and treatment response. The mathematical model integrates the continuum field of variables with a discrete approach and incorporates the random walk method for individual cell migration. By tracking the moving boundary of tumoroids, the HDC model separates volumetric growth from invasion. Invasion direction asymmetries were incorporated into the m...

Amplitude-dependent rheological responses of axisymmetric grains

Europhysics Letters

Oscillatory shear flows of axisymmetric grains exhibit amplitude-dependent rheological responses,... more Oscillatory shear flows of axisymmetric grains exhibit amplitude-dependent rheological responses, which is related to the evolution of the microstructure. In this work, it is shown that the highly ordered configuration of grains at steady-state shear flow undergoes microstructural rearrangement when subjected to shear oscillations. This rearrangement may lead to reduced ordering configurations which give rise to macroscale shear hardening, which can result in shear jamming if the applied shear traction is below the critical shear resistance. On the other hand, it was observed that applying oscillatory shear to the primary condensed shear flow enhances flowability due to microstructure rearrangement. In this study, we investigate the amplitude-dependent rheological responses of axisymmetric grains subjected oscillatory shear flows. First, we look into the evolution of grains alignment subjected to a range of oscillation amplitudes, where we show that the lower oscillation amplitudes ...

Mathematical Modeling of Spherical Shell-Type Pattern of Tumor Invasion

Symmetry

Cancer cell migration, as the principal element of tumor invasion, involves different cellular me... more Cancer cell migration, as the principal element of tumor invasion, involves different cellular mechanisms. Various modes of cell migration including single and collective motions contribute to the invasion patterns. The competition between adhesive cell–cell and cell–matrix forces is a key factor that determines such patterns. In this paper, we study a distinct shell-type mode of tumor invasion observed in brain and breast tumors. In this mode, cells at the outer layer of the tumor collectively move away from the core and form a shell-type shape. Both the core and the shell sustain a sharp interface between cells and the surrounding matrix. To model the preserved interface, we adopted a Cahn–Hilliard-type free energy relation with the contribution of the interfacial stress. This nonconvex form of free energy allows for cells to remain together and preserve the tumor core via adhesive cell–cell forces while separating the core from the surrounding matrix across a continuous sharp int...

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A multi-omics analysis of glioma chemoresistance using a hybrid microphysiological model of glioblastoma

Chemoresistance is a major clinical challenge in the management of glioblastoma (GBM) Temozolomid... more Chemoresistance is a major clinical challenge in the management of glioblastoma (GBM) Temozolomide (TMZ) is the chemotherapeutic drug of choice for GBM; however, the therapeutic effect of TMZ is limited due to the development of resistance. Recapitulating GBM chemoresistance in a controlled environment is thus essential in understanding the mechanism of chemoresistance. Herein, we present a hybrid microphysiological model of chemoresistant GBM-on-a-chip (HGoC) by directly co-culturing TMZ-resistant GBM spheroids with healthy neurons to mimic the microenvironment of both the tumor and the surrounding healthy tissue. We characterized the model with proteomics, lipidomics, and secretome assays. The results showed that our artificial model recapitulated the molecular signatures of recurrent GBM in humans. Both showed alterations in vesicular transport and cholesterol pathways, mitotic quiescence, and a switch in metabolism to oxidative phosphorylation associated with a transition from m...

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In Vitro Brain Organoids and Computational Models to Study Cell Death in Brain Diseases

Methods in molecular biology, 2022

In-Silico Study of Asymmetric Remodeling of Tumors in Response to External Biochemical Stimuli

Among different hallmarks of cancer, understanding biomechanics of tumor growth and remodeling be... more Among different hallmarks of cancer, understanding biomechanics of tumor growth and remodeling benefits the most from the theoretical framework of continuum mechanics. Tumor remodeling initiates when cancer cells seek new homeostasis in response to the microenvironmental stimuli. Cells within a growing tumor are capable to remodel their inter- and intraconnections and become more mobile to achieve a new homeostasis. This mobility enables the tumor to undergo large deformation. In this work, we studied the remodeling in the context of continuum mechanics. We developed an evolution law for the remodeling-associated deformation which correlates the remodeling to a characteristic tensor of external stimuli. The asymmetric remodeling and the induced mechanical stresses were analyzed for different types of biochemical distributions. To experimentally investigate the model, we studied the remodeling of human glioblastoma (hGB) tumoroids in response to the gradient of nutrients. Using a tum...

A New Venting Valve for Anti-colic Nursing Bottles

CMBES Proceedings, May 11, 2021

Orientational-induced strain hardening of axisymmetric grains

Physical review, Oct 3, 2022

Design and modeling of a novel translational and angular micro-electromechanical accelerometer

Aerospace Science and Technology, 2016

A continuous model is presented for a combined translational/angular micro capacitive acceleromet... more A continuous model is presented for a combined translational/angular micro capacitive accelerometer. New design includes two rectangular micro-beams, square shaped proof mass and four pairs of parallel capacitors, which are located in an appropriate construction. In order to find the transverse/torsional vibration effects of micro-beams on the proof mass, the Euler-Bernoulli beam theory is used to derive the governing partial differential equations of the problem which are then solved using modal analysis. Effects of squeeze film on the motion of the proof mass, including both spring and dissipative forces/moments, are considered using nonlinear isothermal Reynold's equation. Afterwards, these equations are solved using HPM method. Electrostatic forces/moments of capacitors are also included in the modeling analysis. Finally, the system of two second-order time-dependent differential equations is obtained. Appropriate formulation in order to correlate the output voltages of the system to the actual input accelerations is presented. Furthermore, output responses are precisely calibrated to form input accelerations. Results for different types of inputs are delineated as five case studies. Apart from transient part of the responses, the model predictions for both angular and translational accelerations show reasonably acceptable convergence with input accelerations of the system. Moreover, results revealed that for various combinations of input accelerations, the system presents reasonably accurate output predictions for each one.

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Non-destructive mechanical assessment for optimization of 3D bioprinted soft tissue scaffolds

iScience

Asymmetric Growth of Tumor Spheroids in a Symmetric Environment

Mathematics

In this work, we studied the stability of radially symmetric growth in tumor spheroids using a re... more In this work, we studied the stability of radially symmetric growth in tumor spheroids using a reaction-diffusion model. In this model, nutrient concentration and internal pressure are local variables that implicitly relate the proliferation of cells to the growth of the tumor. The analytical solution of the governing model was presented in an orthonormal spherical harmonic basis. It was shown that the radially symmetric steady-state solution to the growth of tumor spheroids, under symmetric growth conditions, was unstable with respect to small asymmetric perturbations. Such perturbations excited the asymmetric modes of growth, which could grow in time and change the spherical configuration of the tumor. The number of such modes and their rates of growth depended on parameters such as surface tension, external energy and the rate of nutrient consumption. This analysis indicated that the spherical configuration of tumor spheroids, even under experimentally controlled symmetric growth...

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Fabrication of palladium functionalized sol-gel based SnO2 gas sensor for H2 and CO detection

2017 IEEE SENSORS, 2017

This study presents design, micro-fabrication and neural network calibration of a low cost micro-... more This study presents design, micro-fabrication and neural network calibration of a low cost micro-gas sensor. This sensor is able to identify two gases (CO and H2) and their concentrations in a mixture. Using the micro-fabrication process the sensitivity of the sensors has increased while decreasing the fabrication cost. Using the Pechini route technique, the sensing layer is fabricated based on a layer of metal oxide semiconductor (SnO2) which is doped with palladium. Sensing layer surface morphology has been characterized (using Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), and X-Ray Diffraction (XRD)) to study (i) the molecular structure of the sensing layer fabricated under various conditions, and (ii) the effect of palladium doping on the crystalline structure. Following our previous study, the neural network calibration is employed to perform identification process. Four different concentrations of Co and H2 are exposed to the fabricated sensor and the results of output voltages show the high sensitivity of the sensing layer.

Role of apoptosis, autophagy, and the unfolded protein response in glioblastoma chemoresistance

Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies, 2021

Glioblastoma (GBM) is a rapidly progressive form of brain tumor with high mortality rates. Curren... more Glioblastoma (GBM) is a rapidly progressive form of brain tumor with high mortality rates. Current treatment modalities are moderately effective and chemoresistance has become a major concern in GBM treatment. Evidence suggests that cross talks between several pathways, including apoptosis, autophagy, and unfolded protein response (UPR), are involved in the induction of resistance to chemotherapeutic agents such as temozolomide (TMZ). Apoptosis is crucial for organism survival through the elimination of unwanted cells. Various conditions such as hypoxia, defective DNA mismatch repair (MMR) system, p53 loss of function, insufficient O6-methylguanine-DNA-methyltransferase (MGMT) enzyme, and dysregulation of miRNAs expression negatively influence apoptosis and lead to chemoresistance. A dual role has been reported for autophagy in GBM chemoresistance and chemosensitivity. Similarly, the UPR adaptive pathway has both cytotoxic and cytoprotective effects on GBM cells in response to chemo...

Bioengineered tissue models for the development of dynamic immuno-associated tumor models and high-throughput immunotherapy cytotoxicity assays

Drug Discovery Today, 2021

Cancer immunotherapy is rapidly developing, with numerous therapies approved over the past decade... more Cancer immunotherapy is rapidly developing, with numerous therapies approved over the past decade and more therapies expected to gain approval in the future. However, immunotherapy of solid tumors has been less successful because immunosuppressive barriers limit immune cell trafficking and function against cancer cells. Interactions between suppressive immune cells, cytokines, and inhibitory factors are central to cancer immunotherapy approaches. In this review, we discuss recent advances in utilizing microfluidic platforms for understanding cancer-suppressive immune system interactions. Dendritic cell (DC)-mediated tumor models, infiltrated lymphocyte-mediated tumor models [e.g., natural killer (NK) cells, T cells, chimeric antigen receptor (CAR) T cells, and macrophages], monocyte-mediated tumor models, and immune checkpoint blockade (ICB) tumor models are among the various bioengineered immune cell-cancer cell interactions that we reviewed herein.

A generalized model for dense axisymmetric grains flow with orientational diffusion

Journal of Fluid Mechanics, 2022

The flow of non-spherical grains is strongly affected by the orientation of the grains, as observ... more The flow of non-spherical grains is strongly affected by the orientation of the grains, as observed in experiments and simulations. An existing model that predicts the orientation of grains as a function of the flow field and shape of the grains, is limited to homogenous orientational fields where the interaction of the grains with their surroundings is negligible. To address this limitation, we generalized the model to account for inhomogeneous orientational fields in the form of spatial non-convective orientational flux. The orientational flux accounts for the interactions of grains with their surroundings and the boundaries. The proposed model is used to study the influence of orientational diffusion and boundary conditions on the flow of dense granular material down an incline. It is shown that the boundary conditions can play a significant role in the orientation of grains in such flows.

Role of apoptosis, autophagy, and the unfolded protein response in glioblastoma chemoresistance

Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies, 2021

Glioblastoma (GBM) is a rapidly progressive form of brain tumor with high mortality rates. Curren... more Glioblastoma (GBM) is a rapidly progressive form of brain tumor with high mortality rates. Current treatment modalities are moderately effective and chemoresistance has become a major concern in GBM treatment. Evidence suggests that cross talks between several pathways, including apoptosis, autophagy, and unfolded protein response (UPR), are involved in the induction of resistance to chemotherapeutic agents such as temozolomide (TMZ). Apoptosis is crucial for organism survival through the elimination of unwanted cells. Various conditions such as hypoxia, defective DNA mismatch repair (MMR) system, p53 loss of function, insufficient O6-methylguanine-DNA-methyltransferase (MGMT) enzyme, and dysregulation of miRNAs expression negatively influence apoptosis and lead to chemoresistance. A dual role has been reported for autophagy in GBM chemoresistance and chemosensitivity. Similarly, the UPR adaptive pathway has both cytotoxic and cytoprotective effects on GBM cells in response to chemo...

Fabrication of palladium functionalized sol-gel based SnO2 gas sensor for H2 and CO detection

2017 IEEE SENSORS, 2017

This study presents design, micro-fabrication and neural network calibration of a low cost micro-... more This study presents design, micro-fabrication and neural network calibration of a low cost micro-gas sensor. This sensor is able to identify two gases (CO and H2) and their concentrations in a mixture. Using the micro-fabrication process the sensitivity of the sensors has increased while decreasing the fabrication cost. Using the Pechini route technique, the sensing layer is fabricated based on a layer of metal oxide semiconductor (SnO2) which is doped with palladium. Sensing layer surface morphology has been characterized (using Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), and X-Ray Diffraction (XRD)) to study (i) the molecular structure of the sensing layer fabricated under various conditions, and (ii) the effect of palladium doping on the crystalline structure. Following our previous study, the neural network calibration is employed to perform identification process. Four different concentrations of Co and H2 are exposed to the fabricated sensor an...

Coupled Torsional and Transverse Vibration Analysis of Panels Partially Supported by Elastic Beam

ArXiv, 2021

This study presents torsional and transverse vibration analysis of a solar panel including a rect... more This study presents torsional and transverse vibration analysis of a solar panel including a rectangular thin plate locally supported by an elastic beam. The plate is totally free in all boundaries, except for the local part attached to the beam. The response of the system, which is subjected to a combination of torsional and transverse vibration, identifies with a couple of PDEs developed by the Euler-Bernoulli assumption and classical plate theory. To calculate the system's natural frequencies, the domain of the solution is discretized by zeroes of the Chebyshev polynomials to apply the Modified Generalized Differential Quadrature method (MGDQ). Furthermore, governing equations along with continuity and boundary conditions are discretized. After obtaining solutions to the eigenvalue problem, several studies are investigated to validate the accuracy of the proposed method. As can be concluded from the tables, MGDQ improves the accuracy of results obtained by GDQ. Results for va...

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Microfluidic-Based Oxygen (O2) Sensors for On-Chip Monitoring of Cell, Tissue and Organ Metabolism

Biosensors

Oxygen (O2) quantification is essential for assessing cell metabolism, and its consumption in cel... more Oxygen (O2) quantification is essential for assessing cell metabolism, and its consumption in cell culture is an important indicator of cell viability. Recent advances in microfluidics have made O2 sensing a crucial feature for organ-on-chip (OOC) devices for various biomedical applications. OOC O2 sensors can be categorized, based on their transducer type, into two main groups, optical and electrochemical. In this review, we provide an overview of on-chip O2 sensors integrated with the OOC devices and evaluate their advantages and disadvantages. Recent innovations in optical O2 sensors integrated with OOCs are discussed in four main categories: (i) basic luminescence-based sensors; (ii) microparticle-based sensors; (iii) nano-enabled sensors; and (iv) commercial probes and portable devices. Furthermore, we discuss recent advancements in electrochemical sensors in five main categories: (i) novel configurations in Clark-type sensors; (ii) novel materials (e.g., polymers, O2 scavengin...

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3D Bioprinting Stem Cell Derived Tissues

Stem cells offer tremendous promise for regenerative medicine as they can become a variety of cel... more Stem cells offer tremendous promise for regenerative medicine as they can become a variety of cell types. They also continuously proliferate, providing a renewable source of cells. Recently, it has been found that 3D printing constructs using stem cells, can generate models representing healthy or diseased tissues, as well as substitutes for diseased and damaged tissues. Here, we review the current state of the field of 3D printing stem cell derived tissues. First, we cover 3D printing technologies and discuss the different types of stem cells used for tissue engineering applications. We then detail the properties required for the bioinks used when printing viable tissues from stem cells. We give relevant examples of such bioprinted tissues, including adipose tissue, blood vessels, bone, cardiac tissue, cartilage, heart valves, liver, muscle, neural tissue, and pancreas. Finally, we provide future directions for improving the current technologies, along with areas of focus for futur...

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