The rearrangement of co-cultured cellular model systems via collective cell migration

Pajić‐Lijaković, Ivana; Eftimie, Raluca; Milivojević, Milan; Bordas, Stéphane

doi:10.1016/j.semcdb.2022.10.002

Cited by 10 publications

(4 citation statements)

References 77 publications

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“…8), the wound closure slows down before accelerating. This could be interpreted as an overcrowd phenomenon [25], and reinforce the hypothesis of CIL in healthy fibroblast. Even with a larger error, this phenomenon is reproduced by our model.…”

Section: Discussionsupporting

confidence: 82%

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Data-driven simple agent-based model of scratch assays on healthy and keloid fibroblasts

Urcun,

Rolin,

Eftimie

et al. 2024

Preprint

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In this study we propose a novel agent-based model to reproduce and propose new hypotheses on the biological mechanisms of cell-cell interactions and cell migration from data obtained during scratch assay with healthy and keloid fibroblasts. The advantage of the agent-based model we propose in this paper lies in its simplicity: only three governing parameters. We conducted a parametric sensitivity analysis and we incorporated the evaluation of contact inhibition of locomotion, aligning with the observed loss during malignant invasion. To study invasion modalities, we conducted in vitro wound healing assays using healthy and pseudo-tumoral (keloid) fibroblasts under diverse conditions: control, macrophage type 1 secretome, and macrophage type 2 secretome. Mitomycin inhibition of proliferation isolated the contribution of migration to wound filling. Our agent-based mathematical model describes configurations based on our microscopy imaging and statistical data, which enables quantitative comparisons between our experimental and numerical results. Calibration and evaluation were performed on the same experiments, enriched by external datasets. With only three governing parameters, our model not only demonstrated good agreement (8.78% to 18.75% error) with external evaluation datasets for all experimental configurations but also provided us with a nuanced understanding of keloid fibroblast behavior during wound healing, especially regarding contact inhibition dynamics.

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Section: Discussionsupporting

confidence: 82%

“…in [24], they highlight that pathological invasive behavior which occurs in cancer or keloid is characterized by the loss of CIL. This concept belongs to collective cells migration modeling, reviewed in [25].…”

Section: Introductionmentioning

confidence: 99%

Data-driven simple agent-based model of scratch assays on healthy and keloid fibroblasts

Urcun,

Rolin,

Eftimie

et al. 2024

Preprint

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“…Cell shear residual stress represents the product of natural and forced convections. While natural convection is caused by the interfacial tension gradient established at the biointerfaces between the pseudo-phases, the forced convection is induced by CCM (Pajic-Lijakovic et al, 2023a, 2023b). The normal and shear residual stress per pseudo-phases are formulated in the Appendix A.…”

Section: The Segregation Of Co-cultured Cellular Systems: Modeling Co...mentioning

confidence: 99%

“…Cadherins are also involved in a variety of cellular processes, including polarity and gene expression (Barriga and Mayor, 2019). Cumulative effects of homotypic cell–cell interactions along the monocultured cellular surfaces in contact with surrounding liquid medium influence the macroscopic tissue surface tension, while the cumulative effects of heterotypic cell–cell interactions along the biointerface established between two cell subpopulations within co-cultured systems influence the macroscopic interfacial tension (Pajic-Lijakovic and Milivojevic, 2023; Pajic-Lijakovic et al, 2023a). These two physical parameters, tissue surface tension and interfacial tension, depend on the type and strength of cell–cell adhesion contacts, cell contractility (Devanny et al, 2021), and extension or compression of multicellular system caused by CCM (Guevorkian et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Segregation of co-cultured multicellular systems: review and modeling consideration

Pajic-Lijakovic,

Eftimie,

Milivojevic

et al. 2024

Quart. Rev. Biophys.

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Cell segregation caused by collective cell migration (CCM) is crucial for morphogenesis, functional development of tissue parts, and is an important aspect in other diseases such as cancer and its metastasis process. Efficiency of the cell segregation depends on the interplay between: (1) biochemical processes such as cell signaling and gene expression and (2) physical interactions between cells. Despite extensive research devoted to study the segregation of various co-cultured systems, we still do not understand the role of physical interactions in cell segregation. Cumulative effects of these physical interactions appear in the form of physical parameters such as: (1) tissue surface tension, (2) viscoelasticity caused by CCM, and (3) solid stress accumulated in multicellular systems. These parameters primarily depend on the interplay between the state of cell-cell adhesion contacts and cell contractility. The role of these physical parameters on the segregation efficiency is discussed on model systems such as co-cultured breast cell spheroids consisting of two subpopulations that are in contact. This review study aims to: (1) summarize biological aspects related to cell segregation, mechanical properties of cell collectives, effects along the biointerface between cell subpopulations and (2) describe from a biophysical/mathematical perspective the same biological aspects summarized before. So that overall it can illustrate the complexity of the biological systems that translate into very complex biophysical/mathematical equations. Moreover, by presenting in parallel these two seemingly different parts (biology vs. equations), this review aims to emphasize the need for experiments to estimate the variety of parameters entering the resulting complex biophysical/mathematical models.

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Active wetting of epithelial tissues: modeling considerations

Pajić‐Lijaković

Milivojević

2023

Eur Biophys J

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The rearrangement of co-cultured cellular model systems via collective cell migration

Cited by 10 publications

References 77 publications

Data-driven simple agent-based model of scratch assays on healthy and keloid fibroblasts

Data-driven simple agent-based model of scratch assays on healthy and keloid fibroblasts

Segregation of co-cultured multicellular systems: review and modeling consideration

Active wetting of epithelial tissues: modeling considerations

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