How cellular movement determines the collective force generated by the Dictyostelium discoideum slug

Dallon, John C.; Othmer, Hans G.

doi:10.1016/j.jtbi.2004.06.015

Cited by 106 publications

(133 citation statements)

References 59 publications

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“…This implies that cells transmit their motive forces through the other cells to the extracellular matrix and that cell-cell adhesion must be an important component in coupling the cytoskeletons of cells ( figure 11). This mode of movement effectively leads to the generation of local body forces which have been the basis for various continuous and discrete models for slug migration [117,118]. So far, these models have ignored the role of the slime sheath in this process which will need to be addressed in further work.…”

Section: Rsfsroyalsocietypublishingorg Interface Focus 6: 20160047mentioning

confidence: 99%

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

2016

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Movement of cells and tissues is a basic biological process that is used in development, wound repair, the immune response to bacterial invasion, tumour formation and metastasis, and the search for food and mates. While some cell movement is random, directed movement stimulated by extracellular signals is our focus here. This involves a sequence of steps in which cells first detect extracellular chemical and/or mechanical signals via membrane receptors that activate signal transduction cascades and produce intracellular signals. These intracellular signals control the motile machinery of the cell and thereby determine the spatial localization of the sites of force generation needed to produce directed motion. Understanding how force generation within cells and mechanical interactions with their surroundings, including other cells, are controlled in space and time to produce cell-level movement is a major challenge, and involves many issues that are amenable to mathematical modelling.

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Section: Rsfsroyalsocietypublishingorg Interface Focus 6: 20160047mentioning

confidence: 99%

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

2016

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“…Cells at the leading edge do not depend on neighboring cells for active migration-they transmit the active force directly to the substrate. The model can easily be extended to incorporate active forces generated by all cells, but under normal conditions the cells in the interior of an aggregate do no useful work toward moving the aggregate if they cannot connect to the surrounding medium (Dallon and Othmer 2004). Thus, in the current model a combination of active movement by the leading-edge cells and passive growth produces the collective motion.…”

Section: The Cell-based Modelmentioning

confidence: 99%

“…(16) yields the trajectory of cell i. For further details concerning the definition and representation of the forces, see Dallon and Othmer (2004) and Kim et al (2007). In collective migration of tumor cells that penetrate the basal membrane, the leading-edge cells create a proteolytic microtrack of locally-degraded ECM (Zone 1 in Fig.…”

Section: The Cell-based Modelmentioning

confidence: 99%

A Hybrid Model of Tumor–Stromal Interactions in Breast Cancer

Kim

Othmer

2013

Bull Math Biol

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Ductal carcinoma in situ (DCIS) is an early stage noninvasive breast cancer that originates in the epithelial lining of the milk ducts, but it can evolve into comedo DCIS and ultimately, into the most common type of breast cancer, invasive ductal carcinoma. Understanding the progression and how to effectively intervene in it presents a major scientific challenge. The extracellular matrix (ECM) surrounding a duct contains several types of cells and several types of growth factors that are known to individually affect tumor growth, but at present the complex biochemical and mechanical interactions of these stromal cells and growth factors with tumor cells is poorly understood. Here we develop a mathematical model that incorporates the cross-talk between stromal and tumor cells, which can predict how perturbations of the local biochemical and mechanical state influence tumor evolution. We focus on the EGF and TGF-β signaling pathways and show how upor down-regulation of components in these pathways affects cell growth and proliferation. We then study a hybrid model for the interaction of cells with the tumor microenvironment (TME), in which epithelial cells (ECs) are modeled individually while the ECM is treated as a continuum, and show how these interactions affect the early development of tumors. Finally, we incorporate breakdown of the epithelium into the model and predict the early stages of tumor invasion into the stroma. Our results shed light on the interactions between growth factors, mechanical properties of the ECM, and feedback signaling loops between stromal and tumor cells, and suggest how epigenetic changes in transformed cells affect tumor progression.

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“…In the hybrid model that is described later we model cells in the proliferating region of the MCTS as deformable ellipses, as was done earlier for the slug stage of the cellular slime mold Dictyostelium discoidium. 42,18 The quiescent and necrotic regions internal to the proliferating region and the extracellular matrix surrounding the spheroid are all modeled as viscoelastic continua (cf. Fig.…”

Section: Introductionmentioning

confidence: 99%

A HYBRID MODEL FOR TUMOR SPHEROID GROWTH IN VITRO I: THEORETICAL DEVELOPMENT AND EARLY RESULTS

Kim

Stolarska

Othmer

2007

Math. Models Methods Appl. Sci.

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Tumor spheroids grown in vitro have been widely used as models of in vivo tumor growth because they display many of the characteristics of in vivo growth, including the effects of nutrient limitations and perhaps the effect of stress on growth. In either case there are numerous biochemical and biophysical processes involved whose interactions can only be understood via a detailed mathematical model. Previous models have focused on either a continuum description or a cell-based description, but both have limitations. In this paper we propose a new mathematical model of tumor spheroid growth that incorporates both continuum and cell-level descriptions, and thereby retains the advantages of each while circumventing some of their disadvantages. In this model the cell-based description is used in the region where the majority of growth and cell division occurs, at the periphery of a tumor, while a continuum description is used for the quiescent and necrotic zones of the tumor and for the extracellular matrix. Reaction-diffusion equations describe the transport and consumption of two important nutrients, oxygen and glucose, throughout the entire domain. The cell-based component of this hybrid model allows us to examine the effects of cell-cell adhesion and variable growth rates at the cellular level rather than at the continuum level. We show that the model can predict a number of cellular behaviors that have been observed experimentally.

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How cellular movement determines the collective force generated by the Dictyostelium discoideum slug

Cited by 106 publications

References 59 publications

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

Progress and perspectives in signal transduction, actin dynamics, and movement at the cell and tissue level: lessons fromDictyostelium

A Hybrid Model of Tumor–Stromal Interactions in Breast Cancer

A HYBRID MODEL FOR TUMOR SPHEROID GROWTH IN VITRO I: THEORETICAL DEVELOPMENT AND EARLY RESULTS

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