scholarly journals Mechanical cell competition in heterogeneous epithelial tissues

2019 ◽  
Author(s):  
R. J. Murphy ◽  
P. R. Buenzli ◽  
R. E. Baker ◽  
M. J. Simpson
Keyword(s):  
Cancer Cells ◽  
Discrete Model ◽  
Continuum Model ◽  
Cell Stiffness ◽  
Epithelial Tissue ◽  
Cell Competition ◽  
Practical Applications ◽  
Source Sink ◽  
Heterogeneous Setting ◽  
Proliferative Advantage

AbstractMechanical cell competition is important during tissue development, cancer invasion, and tissue ageing. Heterogeneity plays a key role in practical applications since cancer cells can have different cell stiffness and different proliferation rates than normal cells. To study this phenomenon, we propose a one-dimensional mechanical model of heterogeneous epithelial tissue dynamics that includes cell-length-dependent proliferation and death mechanisms. Proliferation and death are incorporated into the discrete model stochastically and arise as source/sink terms in the corresponding continuum model that we derive. Using the new discrete model and continuum description, we explore several applications including the evolution of homogeneous tissues experiencing proliferation and death, and competition in a heterogeneous setting with a cancerous tissue competing for space with an adjacent normal tissue. This framework allows us to postulate new mechanisms that explain the ability of cancer cells to outcompete healthy cells through mechanical differences rather than by having some intrinsic proliferative advantage. We advise when the continuum model is beneficial and demonstrate why naively adding source/sink terms to a continuum model without considering the underlying discrete model may lead to incorrect results.

scholarly journals A free boundary mechanobiological model of epithelial tissues

2020 ◽  
Author(s):  
Tamara A. Tambyah ◽  
Ryan J. Murphy ◽  
Pascal R. Buenzli ◽  
Matthew J. Simpson
Keyword(s):  
Free Boundary ◽  
Discrete Model ◽  
Continuum Model ◽  
Numerical Solutions ◽  
Tissue Level ◽  
Intracellular Signalling ◽  
Reaction Diffusion Equations ◽  
Epithelial Tissue ◽  
Cell Level ◽  
The Continuum

AbstractIn this study, we couple intracellular signalling and cell–based mechanical properties to develop a novel free boundary mechanobiological model of epithelial tissue dynamics. Mechanobiological coupling is introduced at the cell level in a discrete modelling framework, and new reaction–diffusion equations are derived to describe tissue–level outcomes. The free boundary evolves as a result of the underlying biological mechanisms included in the discrete model. To demonstrate the accuracy of the continuum model, we compare numerical solutions of the discrete and continuum models for two different signalling pathways. First, we study the Rac–Rho pathway where cell– and tissue–level mechanics are directly related to intracellular signalling. Second, we study an activator–inhibitor system which gives rise to spatial and temporal patterning related to Turing patterns. In all cases, the continuum model and free boundary condition accurately reflect the cell–level processes included in the discrete model.

scholarly journals A free boundary mechanobiological model of epithelial tissues

2020 ◽  
Vol 476 (2243) ◽  
pp. 20200528 ◽  
Author(s):  
Tamara A. Tambyah ◽  
Ryan J. Murphy ◽  
Pascal R. Buenzli ◽  
Matthew J. Simpson
Keyword(s):  
Free Boundary ◽  
Discrete Model ◽  
Continuum Model ◽  
Numerical Solutions ◽  
Tissue Level ◽  
Intracellular Signalling ◽  
Reaction Diffusion Equations ◽  
Epithelial Tissue ◽  
Cell Level ◽  
The Continuum

In this study, we couple intracellular signalling and cell-based mechanical properties to develop a novel free boundary mechanobiological model of epithelial tissue dynamics. Mechanobiological coupling is introduced at the cell level in a discrete modelling framework, and new reaction–diffusion equations are derived to describe tissue-level outcomes. The free boundary evolves as a result of the underlying biological mechanisms included in the discrete model. To demonstrate the accuracy of the continuum model, we compare numerical solutions of the discrete and continuum models for two different signalling pathways. First, we study the Rac–Rho pathway where cell- and tissue-level mechanics are directly related to intracellular signalling. Second, we study an activator–inhibitor system which gives rise to spatial and temporal patterning related to Turing patterns. In all cases, the continuum model and free boundary condition accurately reflect the cell-level processes included in the discrete model.

scholarly journals Cell competition between anaplastic thyroid cancer and normal thyroid follicular cells exerts reciprocal stress response defining tumor suppressive effects of normal epithelial tissue

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249059
Author(s):  
Aidana Amrenova ◽  
Keiji Suzuki ◽  
Vladimir Saenko ◽  
Shunichi Yamashita ◽  
Norisato Mitsutake
Keyword(s):  
Thyroid Cancer ◽  
Stress Response ◽  
Cancer Cells ◽  
Anaplastic Thyroid Cancer ◽  
Epithelial Tissue ◽  
Follicular Cells ◽  
Cell Competition ◽  
Normal Cells ◽  
Normal Thyroid ◽  
Thyroid Follicular Cells

The microenvironment of an early-stage tumor, in which a small number of cancer cells is surrounded by a normal counterpart milieu, plays a crucial role in determining the fate of initiated cells. Here, we examined cell competition between anaplastic thyroid cancer cells and normal thyroid follicular cells using co-culture method. Cancer cells were grown until they formed small clusters, to which normal cells were added to create high-density co-culture condition. We found that co-culture with normal cells significantly suppressed the growth of cancer cell clusters through the activation of Akt-Skp2 pathway. In turn, cancer cells triggered apoptosis in the neighboring normal cells through local activation of ERK1/2. A bi-directional cell competition provides a suppressive mechanism of anaplastic thyroid cancer progression. Since the competitive effect was negated by terminal growth arrest caused by radiation exposure to normal cells, modulation of reciprocal stress response in vivo could be an intrinsic mechanism associated with tumor initiation, propagation, and metastasis.

scholarly journals The microRNA-210-Stathmin1 Axis Decreases Cell Stiffness to Facilitate the Invasiveness of Colorectal Cancer Stem Cells

Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1833
Author(s):  
Tsai-Tsen Liao ◽  
Wei-Chung Cheng ◽  
Chih-Yung Yang ◽  
Yin-Quan Chen ◽  
Shu-Han Su ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Cell Motility ◽  
Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Cell Stiffness ◽  
Mesenchymal Transition ◽  
Cytoskeletal Dynamics ◽  
Colorectal Cancer Stem Cells

Cell migration is critical for regional dissemination and distal metastasis of cancer cells, which remain the major causes of poor prognosis and death in patients with colorectal cancer (CRC). Although cytoskeletal dynamics and cellular deformability contribute to the migration of cancer cells and metastasis, the mechanisms governing the migratory ability of cancer stem cells (CSCs), a nongenetic source of tumor heterogeneity, are unclear. Here, we expanded colorectal CSCs (CRCSCs) as colonospheres and showed that CRCSCs exhibited higher cell motility in transwell migration assays and 3D invasion assays and greater deformability in particle tracking microrheology than did their parental CRC cells. Mechanistically, in CRCSCs, microRNA-210-3p (miR-210) targeted stathmin1 (STMN1), which is known for inducing microtubule destabilization, to decrease cell elasticity in order to facilitate cell motility without affecting the epithelial–mesenchymal transition (EMT) status. Clinically, the miR-210-STMN1 axis was activated in CRC patients with liver metastasis and correlated with a worse clinical outcome. This study elucidates a miRNA-oriented mechanism regulating the deformability of CRCSCs beyond the EMT process.

A Review of some Theoretical Models for Point Defect Calculations

2012 ◽  
Vol 329 ◽  
pp. 81-0
Author(s):  
Amitava Ghorai
Keyword(s):  
Point Defect ◽  
Discrete Model ◽  
Continuum Model ◽  
Theoretical Models ◽  
Jellium Model ◽  
Main Thrust ◽  
Lattice Statics ◽  
Bond Model ◽  
Model Lattice ◽  
Model Continuum

A Brief Sketch of Different Models for the Calculation of Defect Parameters in Metals and Alloys, Comparison of Data and Limitations Has Been Reviewed here; Especially Relaxations due to a Vacancy Type of Point Defect, its Formation, Migration, Activation Energies and Related other Parameters Based upon the Present Experimental Status. the Models Reviewed Are the Bond Model, Continuum Model, Semi-Discrete Model, Jellium Model, Thermodynamic Model, Lattice Statics Model, Atomistic Continuum Model and Pseudopotential Model. the Main Thrust Concerns the Last Model. the Taylor, Vashishta and Singwi, Harrison, Kleinmann and King and Kutler Form of Exchange and Correlation Function Are Almost Similar, Give Moderate Results and May Be Trusted for Better Results.

Thermo-structural analysis of a honeycomb-type volumetric absorber for concentrated solar power applications

2021 ◽  
Vol ahead-of-print (ahead-of-print) ◽  
Author(s):  
Masoud Behzad ◽  
Benjamin Herrmann ◽  
Williams R. Calderón-Muñoz ◽  
José M. Cardemil ◽  
Rodrigo Barraza
Keyword(s):  
Heat Transfer ◽  
Thermal Stress ◽  
Steady State ◽  
Discrete Model ◽  
Continuum Model ◽  
Transient State ◽  
Operating Conditions ◽  
Steady State Condition ◽  
Content Type ◽  
The Continuum

Purpose Volumetric air receivers experience high thermal stress as a consequence of the intense radiation flux they are exposed to when used for heat and/or power generation. This study aims to propose a proper design that is required for the absorber and its holder to ensure efficient heat transfer between the fluid and solid phases and to avoid system failure due to thermal stress. Design/methodology/approach The design and modeling processes are applied to both the absorber and its holder. A multi-channel explicit geometry design and a discrete model is applied to the absorber to investigate the conjugate heat transfer and thermo-mechanical stress levels present in the steady-state condition. The discrete model is used to calibrate the initial state of the continuum model that is then used to investigate the transient operating states representing cloud-passing events. Findings The steady-state results constitute promising findings for operating the system at the desired airflow temperature of 700°C. In addition, we identified regions with high temperatures and high-stress values. Furthermore, the transient state model is capable of capturing the heat transfer and fluid dynamics phenomena, allowing the boundaries to be checked under normal operating conditions. Originality/value Thermal stress analysis of the absorber and the steady/transient-state thermal analysis of the absorber/holder were conducted. Steady-state heat transfer in the explicit model was used to calibrate the initial steady-state of the continuum model.

scholarly journals Active elimination of intestinal cells drives oncogenic growth in organoids

2020 ◽  
Author(s):  
Ana Krotenberg Garcia ◽  
Arianna Fumagalli ◽  
Huy Quang Le ◽  
Owen J. Sansom ◽  
Jacco van Rheenen ◽  
...  
Keyword(s):  
Quality Control ◽  
Cell Death ◽  
Cancer Cells ◽  
Cell Fate ◽  
Crucial Role ◽  
Intestinal Cells ◽  
Dependent Manner ◽  
Wild Type ◽  
Cell Competition ◽  
Type Population

AbstractCompetitive cell-interactions play a crucial role in quality control during development and homeostasis. Here we show that cancer cells use such interactions to actively eliminate wild-type intestine cells in enteroid monolayers and organoids. This apoptosis-dependent process boosts proliferation of intestinal cancer cells. The remaining wild-type population activates markers of primitive epithelia and transits to a fetal-like state. Prevention of this cell fate transition avoids elimination of wild-type cells and, importantly, limits the proliferation of cancer cells. JNK signalling is activated in competing cells and is required for cell fate change and elimination of wild-type cells. Thus, cell competition drives growth of cancer cells by active out-competition of wild-type cells through forced cell death and cell fate change in a JNK dependent manner.

scholarly journals Murray’s law for discrete and continuum models of biological networks

2019 ◽  
Vol 29 (12) ◽  
pp. 2359-2376
Author(s):  
Jan Haskovec ◽  
Peter Markowich ◽  
Giulia Pilli
Keyword(s):  
Biological Networks ◽  
Discrete Model ◽  
Continuum Model ◽  
Transportation Network ◽  
Continuum Models ◽  
Scaling Relation ◽  
Murray's Law ◽  
Murray’S Law ◽  
Rectangular Mesh ◽  
The Continuum

We demonstrate the validity of Murray’s law, which represents a scaling relation for branch conductivities in a transportation network, for discrete and continuum models of biological networks. We first consider discrete networks with general metabolic coefficient and multiple branching nodes and derive a generalization of the classical 3/4-law. Next we prove an analogue of the discrete Murray’s law for the continuum system obtained in the continuum limit of the discrete model on a rectangular mesh. Finally, we consider a continuum model derived from phenomenological considerations and show the validity of the Murray’s law for its linearly stable steady states.

Modeling Flow and Transport in Fractured Crystalline Rock using the Discrete Fracture Network Concept

1988 ◽  
Vol 127 ◽  
Author(s):  
Björn Dverstorp ◽  
Wille Nordqvist ◽  
Johan Andersson
Keyword(s):  
Discrete Model ◽  
Continuum Model ◽  
Large Scale ◽  
Flow Analysis ◽  
Flow Distribution ◽  
Crystalline Rock ◽  
Discrete Models ◽  
Large Variability ◽  
Rock Heterogeneity ◽  
Modeling Flow

ABSTRACTThe conductive properties of fractured crystalline rock vary considerably in space, which implies that the flow is very unevenly distributed in space. The large variability raises doubts on modeling the flow with a large scale continuum model. Modeling flow in fractured crystalline rock in a network of discrete fractures provides an increased understanding of the character of the rock heterogeneity. Compared to a continuum model discrete models introduce new parameters such as statistical distributions for fracture orientation, radii, density and transmissivity that need to be estimated. By analyzing the migration experiment in the Stripa research mine in Sweden it is demonstrated how to calibrate and eventually validate a discrete model on field data. The flow analysis shows that the flow distribution on the drift roof and in two out of three vertical boreholes can be modelled with the same discrete model. The properties of the third borehole differ substantially. Initial attempts of analyzing the tracer experiment are also described.

New Cell Cycle Inhibitors Target Aneuploidy in Cancer Therapy

2019 ◽  
Vol 59 (1) ◽  
pp. 361-377 ◽  
Author(s):  
Masanori Kawakami ◽  
Xi Liu ◽  
Ethan Dmitrovsky
Keyword(s):  
Cancer Cells ◽  
Chromosome Segregation ◽  
Antineoplastic Agents ◽  
Spindle Assembly Checkpoint ◽  
Critical Level ◽  
New Agents ◽  
Chromosome Missegregation ◽  
Diploid Cells ◽  
Cell Cycle Inhibitors ◽  
Proliferative Advantage

Aneuploidy is a hallmark of cancer. Defects in chromosome segregation result in aneuploidy. Multiple pathways are engaged in this process, including errors in kinetochore-microtubule attachments, supernumerary centrosomes, spindle assembly checkpoint (SAC) defects, and chromosome cohesion defects. Although aneuploidy provides an adaptation and proliferative advantage in affected cells, excessive aneuploidy beyond a critical level can be lethal to cancer cells. Given this, enhanced chromosome missegregation is hypothesized to limit survival of aneuploid cancer cells, especially when compared to diploid cells. Based on this concept, proteins and pathways engaged in chromosome segregation are being exploited as candidate therapeutic targets for aneuploid cancers. Agents that induce chromosome missegregation and aneuploidy now exist, including SAC inhibitors, those that alter centrosome fidelity and others that are under active study in preclinical and clinical contexts. This review explores the therapeutic potentials of such new agents, including the benefits of combining them with other antineoplastic agents.

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