Effect of an osmotic stress on multicellular aggregates

Monnier, Sylvain; Delarue, Morgan; Brunel, Benjamin; Dolega, Monika E.; Delon, Antoine; Cappello, Giovanni

doi:10.1016/j.ymeth.2015.07.009

Cited by 51 publications

(67 citation statements)

References 28 publications

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“…In a growing tumor, an increasing cell density generates a compressive mechanical stress which would likely lead to an increasing mechanical obstacle for mitotic rounding. Indeed, mechanical confinement or external pressure have been shown to hamper cell proliferation in tumor spheroids [14][15][16][17][18] . Thus, it has been hypothesized that the actin cortex of cancer cells exhibits oncogenic adaptations that allow for ongoing mitotic rounding and division inside tumors 19 .…”

Section: Introductionmentioning

confidence: 99%

EMT-induced cell mechanical changes enhance mitotic rounding strength

Hosseini

Taubenberger

Werner

et al. 2019

Preprint

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To undergo mitosis successfully, most animal cells need to acquire a round shape to provide space for the mitotic spindle. This mitotic rounding relies on mechanical deformation of surrounding tissue and is driven by forces emanating from actomyosin contractility. Cancer cells are able to maintain successful mitosis in mechanically challenging environments such as the increasingly crowded environment of a growing tumor, thus, suggesting an enhanced ability of mitotic rounding in cancer. Here, we show that epithelial mesenchymal transition (EMT), a hallmark of cancer progression and metastasis, gives rise to a cell-cycle dependent cellmechanical switch and enhanced mitotic rounding strength in breast epithelial cells. Furthermore, we show that this cell-mechanical change correlates with a strong EMT-induced change in the activity of Rho GTPases RhoA and Rac1. Accordingly, we identify Rac1 as a cell-cycle dependent regulator of actin cortex mechanics. Our findings hint at a new role of EMT in successful mitotic rounding and division in mechanically confined environments such as a growing tumor.

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Section: Introductionmentioning

confidence: 99%

EMT-induced cell mechanical changes enhance mitotic rounding strength

Hosseini

Taubenberger

Werner

et al. 2019

Preprint

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“…For instance, Delarue et al [66,67] conclude from experiments with growing spheroids under pressure that cells are compressible with compression moduli of the order of 10 kP a. On the other hand, the Monnier et al [42] find individual cell compression moduli of several orders of magnitude higher (1 MPa) than the one reported above. Yet, Monnier et al have measured this over short time period and accordingly they further state in their paper that on longer timescales, the compression modulus might differ from that value may due to adaptation of the cell.…”

Section: Calibration Of Dcm Parameters From Optical Stretcher Experimmentioning

confidence: 90%

“…As water transport volume flow rates are small, on short time scales cell volume can be only slightly compressed by compression of the elastic structures inside the cell such as the cytoskeleton, hence the cell exhibits a near incompressible behavior. On longer timescales, the cell response may become more complex due to intracellular adaptations [42]. The force F T,i accounts for resistance of isotropic expansion of the cell membrane.…”

Section: Forces and Equations Of Motionmentioning

confidence: 99%

Quantifying the mechanics and growth of cells and tissues in 3D using high resolution computational models

Neitsch

Johann

et al. 2018

Preprint

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Mathematical models are increasingly designed to guide experiments in biology, biotechnology, as well as to assist in medical decision making. They are in particular important to understand emergent collective cell behavior. For this purpose, the models, despite still abstractions of reality, need to be quantitative in all aspects relevant for the question of interest. The focus in this paper is to study the regeneration of liver after drug-induced depletion of hepatocytes, in which surviving dividing and migrating hepatocytes must squeeze through a blood vessel network to fill the emerged lesions. Here, the cells' response to mechanical stress might significantly impact on the regeneration process. We present a 3D high-resolution cell-based model integrating information from measurements in order to obtain a refined quantitative understanding of the cell-biomechanical impact on the closure of drug-induced lesions in liver. Our model represents each cell individually, constructed as a physically scalable network of viscoelastic elements, capable of mimicking realistic cell deformation and supplying information at subcellular scales. The cells have the capability to migrate, grow and divide, and infer the nature of their mechanical elements and their parameters from comparisons with optical stretcher experiments. Due to triangulation of the cell surface, interactions of cells with arbitrarily shaped (triangulated) structures such as blood vessels can be captured naturally. Comparing our simulations with those of so-called center-based models, in which cells have a rigid shape and forces are exerted between cell centers, we find that the migration forces a cell needs to exert on its environment to close a tissue lesion, is much smaller than predicted by center-based models. This effect is expected to be even more present in chronic liver disease, where tissue stiffens and excess collagen narrows pores for cells to squeeze through.

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“…We compare the effect of a selective compression of cells within the aggregate, leaving the extracellular matrix unstrained, to a global compression of the whole aggregate. We show that the global compression strongly reduces the aggregate volume 9-13 , while the same amount of selective compression on cells has almost no effect 14,15 . We support this finding with a theoretical model of an actively pre-stressed composite material, made of incompressible and impermeable cells and a poroelastic interstitial space.…”

mentioning

confidence: 83%

“…Yet, how the presence of the ECM in multicellular structures determines their mechanical behavior remains to be determined and could be a key factor in some cases. This is exemplified by the fact that the compressibility modulus of individual cells 15 is several orders of magnitude higher than the one of multicellular aggregates of similar cells 22,23 . In this article, we use…”

Section: Introductionmentioning

confidence: 99%

Extracellular Matrix acts as pressure detector in biological tissues

Dolega

Brunel

Goff

et al. 2018

Preprint

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Imposed deformations play an important role in morphogenesis and tissue homeostasis, both in normal andpathological conditions 1-5 . To perceive mechanical perturbations of different types and magnitudes, tissues need a range of appropriate detectors 6-8 , with a compliance that has to match the perturbation amplitude.As a proxy of biological tissues, we use multicellular aggregates, a composite material made of cells, extracellular matrix and permeating fluid. We compare the effect of a selective compression of cells within the aggregate, leaving the extracellular matrix unstrained, to a global compression of the whole aggregate. We show that the global compression strongly reduces the aggregate volume 9-13 , while the same amount of selective compression on cells has almost no effect 14,15 . We support this finding with a theoretical model of an actively pre-stressed composite material, made of incompressible and impermeable cells and a poroelastic interstitial space. This description correctly predicts the emergent bulk modulus of the aggregate as well as the hydrodynamic diffusion coefficient of the percolating interstitial fluid under compression. We further show that, on a longer timescale, the extracellular matrix serves as a sensor that regulates cell proliferation and migration in a 3D environment through its permanent deformation and dehydration following the global compression.

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Effect of an osmotic stress on multicellular aggregates

Cited by 51 publications

References 28 publications

EMT-induced cell mechanical changes enhance mitotic rounding strength

EMT-induced cell mechanical changes enhance mitotic rounding strength

Quantifying the mechanics and growth of cells and tissues in 3D using high resolution computational models

Extracellular Matrix acts as pressure detector in biological tissues

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