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  1. Article: Modelling of Tissue Invasion in Epithelial Monolayers.

    Alsubaie, Faris Saad / Khataee, Hamid / Neufeld, Zoltan

    Life (Basel, Switzerland)

    2023  Volume 13, Issue 2

    Abstract: Mathematical and computational models are used to describe biomechanical processes in multicellular systems. Here, we develop a model to analyse how two types of epithelial cell layers interact during tissue invasion depending on their cellular ... ...

    Abstract Mathematical and computational models are used to describe biomechanical processes in multicellular systems. Here, we develop a model to analyse how two types of epithelial cell layers interact during tissue invasion depending on their cellular properties, i.e., simulating cancer cells expanding into a region of normal cells. We model the tissue invasion process using the cellular Potts model and implement our two-dimensional computational simulations in the software package CompuCell3D. The model predicts that differences in mechanical properties of cells can lead to tissue invasion, even if the division rates and death rates of the two cell types are the same. We also show how the invasion speed varies depending on the cell division and death rates and the mechanical properties of the cells.
    Language English
    Publishing date 2023-02-02
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662250-6
    ISSN 2075-1729
    ISSN 2075-1729
    DOI 10.3390/life13020427
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  2. Article: Modelling the Collective Mechanical Regulation of the Structure and Morphology of Epithelial Cell Layers.

    Khataee, Hamid / Fraser, Madeleine / Neufeld, Zoltan

    Frontiers in cell and developmental biology

    2022  Volume 10, Page(s) 767688

    Abstract: The morphology and function of epithelial sheets play an important role in healthy tissue development and cancer progression. The maintenance of structure of closely packed epithelial layers requires the coordination of various mechanical forces due to ... ...

    Abstract The morphology and function of epithelial sheets play an important role in healthy tissue development and cancer progression. The maintenance of structure of closely packed epithelial layers requires the coordination of various mechanical forces due to intracellular activities and interactions with other cells and tissues. However, a general model for the combination of mechanical properties which determine the cell shape and the overall structure of epithelial layers remains elusive. Here, we propose a computational model, based on the Cellular Potts Model, to analyse the interplay between mechanical properties of cells and dynamical transitions in epithelial cell shapes and structures. We map out phase diagrams as functions of cellular properties and the orientation of cell division. Results show that monolayers of squamous, cuboidal, and columnar cells are formed when the axis of cell proliferation is perpendicular to the substrate or along the major axis of the cells. Monolayer-to-multilayer transition is promoted via cell extrusion, depending on the mechanical properties of cells and the orientation of cell division. The results and model predictions are discussed in the context of experimental observations.
    Language English
    Publishing date 2022-03-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2737824-X
    ISSN 2296-634X
    ISSN 2296-634X
    DOI 10.3389/fcell.2022.767688
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  3. Article ; Online: Targeted adaptive isolation strategy for Covid-19 pandemic

    Zoltan Neufeld / Hamid Khataee

    Abstract: We investigate the effects of social distancing in controlling the impact of the Covid-19 epidemic using a simple SIR epidemic model. We show that an alternative or complementaryapproach based on targeted isolation of the vulnerable subpopulation may ... ...

    Abstract We investigate the effects of social distancing in controlling the impact of the Covid-19 epidemic using a simple SIR epidemic model. We show that an alternative or complementaryapproach based on targeted isolation of the vulnerable subpopulation may provide a moreefficient and robust strategy at a lower economic and social cost within a shorter timeframe.
    Keywords covid19
    Publisher medrxiv
    Document type Article ; Online
    DOI 10.1101/2020.03.23.20041897
    Database COVID19

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  4. Article ; Online: Modelling the Collective Mechanical Regulation of the Structure and Morphology of Epithelial Cell Layers

    Hamid Khataee / Madeleine Fraser / Zoltan Neufeld

    Frontiers in Cell and Developmental Biology, Vol

    2022  Volume 10

    Abstract: The morphology and function of epithelial sheets play an important role in healthy tissue development and cancer progression. The maintenance of structure of closely packed epithelial layers requires the coordination of various mechanical forces due to ... ...

    Abstract The morphology and function of epithelial sheets play an important role in healthy tissue development and cancer progression. The maintenance of structure of closely packed epithelial layers requires the coordination of various mechanical forces due to intracellular activities and interactions with other cells and tissues. However, a general model for the combination of mechanical properties which determine the cell shape and the overall structure of epithelial layers remains elusive. Here, we propose a computational model, based on the Cellular Potts Model, to analyse the interplay between mechanical properties of cells and dynamical transitions in epithelial cell shapes and structures. We map out phase diagrams as functions of cellular properties and the orientation of cell division. Results show that monolayers of squamous, cuboidal, and columnar cells are formed when the axis of cell proliferation is perpendicular to the substrate or along the major axis of the cells. Monolayer-to-multilayer transition is promoted via cell extrusion, depending on the mechanical properties of cells and the orientation of cell division. The results and model predictions are discussed in the context of experimental observations.
    Keywords computational modeling ; tissue modelling ; mechanobiolgy ; cell morphological analysis ; cellular mechanics ; stochastic modelling and simulation ; Biology (General) ; QH301-705.5
    Subject code 612
    Language English
    Publishing date 2022-03-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
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  5. Article ; Online: Effects of social distancing on the spreading of COVID-19 inferred from mobile phone data.

    Khataee, Hamid / Scheuring, Istvan / Czirok, Andras / Neufeld, Zoltan

    Scientific reports

    2021  Volume 11, Issue 1, Page(s) 1661

    Abstract: A better understanding of how the COVID-19 pandemic responds to social distancing efforts is required for the control of future outbreaks and to calibrate partial lock-downs. We present quantitative relationships between key parameters characterizing the ...

    Abstract A better understanding of how the COVID-19 pandemic responds to social distancing efforts is required for the control of future outbreaks and to calibrate partial lock-downs. We present quantitative relationships between key parameters characterizing the COVID-19 epidemiology and social distancing efforts of nine selected European countries. Epidemiological parameters were extracted from the number of daily deaths data, while mitigation efforts are estimated from mobile phone tracking data. The decrease of the basic reproductive number ([Formula: see text]) as well as the duration of the initial exponential expansion phase of the epidemic strongly correlates with the magnitude of mobility reduction. Utilizing these relationships we decipher the relative impact of the timing and the extent of social distancing on the total death burden of the pandemic.
    MeSH term(s) COVID-19/epidemiology ; COVID-19/pathology ; COVID-19/transmission ; COVID-19/virology ; Cell Phone ; Europe/epidemiology ; Geographic Information Systems ; Humans ; Pandemics ; Physical Distancing ; Quarantine ; SARS-CoV-2/isolation & purification ; Travel/statistics & numerical data
    Language English
    Publishing date 2021-01-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-021-81308-2
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  6. Article ; Online: Contact inhibition of locomotion generates collective cell migration without chemoattractants in an open domain.

    Khataee, Hamid / Czirok, Andras / Neufeld, Zoltan

    Physical review. E

    2021  Volume 104, Issue 1-1, Page(s) 14405

    Abstract: Neural crest cells are embryonic stem cells that migrate throughout embryos and, at different target locations, give rise to the formation of a variety of tissues and organs. The directional migration of the neural crest cells is experimentally described ...

    Abstract Neural crest cells are embryonic stem cells that migrate throughout embryos and, at different target locations, give rise to the formation of a variety of tissues and organs. The directional migration of the neural crest cells is experimentally described using a process referred to as contact inhibition of locomotion, by which cells redirect their movement upon the cell-cell contacts. However, it is unclear how the migration alignment is affected by the motility properties of the cells. Here, we theoretically model the migration alignment as a function of the motility dynamics and interaction of the cells in an open domain with a channel geometry. The results indicate that by increasing the influx rate of the cells into the domain a transition takes place from random movement to an organized collective migration, where the migration alignment is maximized and the migration time is minimized. This phase transition demonstrates that the cells can migrate efficiently over long distances without any external chemoattractant information about the direction of migration just based on local interactions with each other. The analysis of the dependence of this transition on the characteristic properties of cellular motility shows that the cell density determines the coordination of collective migration whether the migration domain is open or closed. In the open domain, this density is determined by a feedback mechanism between the flux and order parameter, which characterises the alignment of collective migration. The model also demonstrates that the coattraction mechanism proposed earlier is not necessary for collective migration and a constant flux of cells moving into the channel is sufficient to produce directed movement over arbitrary long distances.
    Language English
    Publishing date 2021-08-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2844562-4
    ISSN 2470-0053 ; 2470-0045
    ISSN (online) 2470-0053
    ISSN 2470-0045
    DOI 10.1103/PhysRevE.104.014405
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  7. Article ; Online: Targeted adaptive isolation strategy for COVID-19 pandemic.

    Neufeld, Zoltan / Khataee, Hamid / Czirok, Andras

    Infectious Disease Modelling

    2020  Volume 5, Page(s) 357–361

    Abstract: We investigate the effects of social distancing in controlling the impact of the COVID-19 epidemic using a simple susceptible-infected-removed epidemic model. We show that an alternative or complementary approach based on targeted isolation of the ... ...

    Abstract We investigate the effects of social distancing in controlling the impact of the COVID-19 epidemic using a simple susceptible-infected-removed epidemic model. We show that an alternative or complementary approach based on targeted isolation of the vulnerable sub-population may provide a more efficient and robust strategy at a lower economic and social cost within a shorter timeframe resulting in a collectively immune population.
    Keywords covid19
    Language English
    Publishing date 2020-06-05
    Publishing country China
    Document type Journal Article
    ZDB-ID 3015225-2
    ISSN 2468-0427 ; 2468-2152
    ISSN (online) 2468-0427
    ISSN 2468-2152
    DOI 10.1016/j.idm.2020.04.003
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  8. Article ; Online: Effects of social distancing on the spreading of COVID-19 inferred from mobile phone data

    Hamid Khataee / Istvan Scheuring / Andras Czirok / Zoltan Neufeld

    Scientific Reports, Vol 11, Iss 1, Pp 1-

    2021  Volume 9

    Abstract: Abstract A better understanding of how the COVID-19 pandemic responds to social distancing efforts is required for the control of future outbreaks and to calibrate partial lock-downs. We present quantitative relationships between key parameters ... ...

    Abstract Abstract A better understanding of how the COVID-19 pandemic responds to social distancing efforts is required for the control of future outbreaks and to calibrate partial lock-downs. We present quantitative relationships between key parameters characterizing the COVID-19 epidemiology and social distancing efforts of nine selected European countries. Epidemiological parameters were extracted from the number of daily deaths data, while mitigation efforts are estimated from mobile phone tracking data. The decrease of the basic reproductive number ( $$R_0$$ R 0 ) as well as the duration of the initial exponential expansion phase of the epidemic strongly correlates with the magnitude of mobility reduction. Utilizing these relationships we decipher the relative impact of the timing and the extent of social distancing on the total death burden of the pandemic.
    Keywords Medicine ; R ; Science ; Q
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
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  9. Article ; Online: Transition from growth to decay of an epidemic due to lockdown.

    Khataee, Hamid / Kibble, Jack / Scheuring, Istvan / Czirok, Andras / Neufeld, Zoltan

    Biophysical journal

    2021  Volume 120, Issue 14, Page(s) 2872–2879

    Abstract: We study the transition of an epidemic from growth phase to decay of the active infections in a population when lockdown health measures are introduced to reduce the probability of disease transmission. Although in the case of uniform lockdown, a simple ... ...

    Abstract We study the transition of an epidemic from growth phase to decay of the active infections in a population when lockdown health measures are introduced to reduce the probability of disease transmission. Although in the case of uniform lockdown, a simple compartmental model would indicate instantaneous transition to decay of the epidemic, this is not the case when partially isolated active clusters remain with the potential to create a series of small outbreaks. We model this using the Gillespie stochastic simulation algorithm based on a connected set of stochastic susceptible-infected-removed/recovered networks representing the locked-down majority population (in which the reproduction number is less than 1) weakly coupled to a large set of small clusters in which the infection may propagate. We find that the presence of such active clusters can lead to slower than expected decay of the epidemic and significantly delayed onset of the decay phase. We study the relative contributions of these changes, caused by the active clusters within the population, to the additional total infected population. We also demonstrate that limiting the size of the inevitable active clusters can be efficient in reducing their impact on the overall size of the epidemic outbreak. The deceleration of the decay phase becomes apparent when the active clusters form at least 5% of the population.
    MeSH term(s) Algorithms ; Computer Simulation ; Disease Outbreaks ; Epidemics ; Humans ; Probability
    Language English
    Publishing date 2021-04-20
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218078-9
    ISSN 1542-0086 ; 0006-3495
    ISSN (online) 1542-0086
    ISSN 0006-3495
    DOI 10.1016/j.bpj.2021.04.004
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  10. Article ; Online: Multiscale modelling of motility wave propagation in cell migration.

    Khataee, Hamid / Czirok, Andras / Neufeld, Zoltan

    Scientific reports

    2020  Volume 10, Issue 1, Page(s) 8128

    Abstract: The collective motion of cell monolayers within a tissue is a fundamental biological process that occurs during tissue formation, wound healing, cancerous invasion, and viral infection. Experiments have shown that at the onset of migration, the motility ... ...

    Abstract The collective motion of cell monolayers within a tissue is a fundamental biological process that occurs during tissue formation, wound healing, cancerous invasion, and viral infection. Experiments have shown that at the onset of migration, the motility is self-generated as a polarisation wave starting from the leading edge of the monolayer and progressively propagates into the bulk. However, it is unclear how the propagation of this motility wave is influenced by cellular properties. Here, we investigate this question using a computational model based on the Potts model coupled to the dynamics of intracellular polarisation. The model captures the propagation of the polarisation wave and suggests that the cells cortex can regulate the migration modes: strongly contractile cells may depolarise the monolayer, whereas less contractile cells can form swirling movement. Cortical contractility is further found to limit the cells motility, which (i) decelerates the wave speed and the leading edge progression, and (ii) destabilises the leading edge. Together, our model describes how different mechanical properties of cells can contribute to the regulation of collective cell migration.
    MeSH term(s) Biomechanical Phenomena ; Cell Movement ; Cell Polarity ; Cell Shape ; Cells/chemistry ; Cells/cytology ; Computer Simulation ; Epithelial Cells/chemistry ; Epithelial Cells/cytology ; Humans ; Models, Biological
    Language English
    Publishing date 2020-05-18
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-020-63506-6
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