Control of cell colony growth by contact inhibition

Schnyder, Simon K.; Molina, John J.; Yamamoto, Ryōichi

doi:10.1038/s41598-020-62913-z

Cited by 35 publications

(28 citation statements)

References 73 publications

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“…Given that cell density appears to affect vortex formation and is known to control contact inhibition of locomotion and proliferation ( Schnyder et al, 2020 ), we explored the spatiotemporal evolution of cell density. Constructing average kymographs in the same way as for speed, radial velocity, and vorticity, we observe that the vortex region in the center of small tissues is accompanied by an unexpected local density minimum ( Figure 4A ).…”

Section: Resultsmentioning

confidence: 99%

Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Heinrich

Alert

LaChance

et al. 2020

eLife

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The coordination of cell proliferation and migration in growing tissues is crucial in development and regeneration but remains poorly understood. Here, we find that, while expanding with an edge speed independent of initial conditions, millimeter-scale epithelial monolayers exhibit internal patterns of proliferation and migration that depend not on the current but on the initial tissue size, indicating memory effects. Specifically, the core of large tissues becomes very dense, almost quiescent, and ceases cell-cycle progression. In contrast, initially-smaller tissues develop a local minimum of cell density and a tissue-spanning vortex. To explain vortex formation, we propose an active polar fluid model with a feedback between cell polarization and tissue flow. Taken together, our findings suggest that expanding epithelia decouple their internal and edge regions, which enables robust expansion dynamics despite the presence of size and history-dependent patterns in the tissue interior.

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Section: Resultsmentioning

confidence: 99%

Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Heinrich

Alert

LaChance

et al. 2020

eLife

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“…Mechanical forces are especially important for normal epithelial homeostasis, and they are often altered in diseases such as cancer, where cellular contractility is modified, and higher compressive forces rise from the confined growth of the tumor 20 , 21 . Furthermore, intercellular contact-induced arrest of cell growth underlies the homeostatic control of cell growth, density, and tissue/organ size 7 , 22 . In recent years, studies on mechanical stretching have been uncovering the cellular responses to strain 23 – 26 .…”

Section: Introductionmentioning

confidence: 99%

Brick Strex: a robust device built of LEGO bricks for mechanical manipulation of cells

Mäntylä

Ihalainen

2021

Sci Rep

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Cellular forces, mechanics and other physical factors are important co-regulators of normal cell and tissue physiology. These cues are often misregulated in diseases such as cancer, where altered tissue mechanics contribute to the disease progression. Furthermore, intercellular tensile and compressive force-related signaling is highlighted in collective cell behavior during development. However, the mechanistic understanding on the role of physical forces in regulation of cellular physiology, including gene expression and signaling, is still lacking. This is partly because studies on the molecular mechanisms of force transmission require easily controllable experimental designs. These approaches should enable both easy mechanical manipulation of cells and, importantly, readouts ranging from microscopy imaging to biochemical assays. To achieve a robust solution for mechanical manipulation of cells, we developed devices built of LEGO bricks allowing manual, motorized and/or cyclic cell stretching and compression studies. By using these devices, we show that $$\upbeta$$ β -catenin responds differentially to epithelial monolayer stretching and lateral compression, either localizing more to the cell nuclei or cell–cell junctions, respectively. In addition, we show that epithelial compression drives cytoplasmic retention and phosphorylation of transcription coregulator YAP1. We provide a complete part listing and video assembly instructions, allowing other researchers to build and use the devices in cellular mechanics-related studies.

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“…The acquired data from the biochemical analyses further indicated that compression induced cleavage of YAP1 but did not affect YAP1 phosphorylation at S127P. Cytoplasmic retention of YAP is associated with suppression of nuclear YAP activity and increased contact inhibition and Hippo signaling 32,63 . Importantly, compression promoted the expression of full-length catenin together with higher molecular weight fractions suggestive of β-catenin membraneassociation and inhibition of β-catenin -mediated growth signaling.…”

Section: Thus These Experiments Indicate That the Concept Can Be Used In Mechanobiological Researchmentioning

confidence: 92%

“…Mechanical forces are especially important for normal epithelial homeostasis and they are often altered in diseases such as cancer, where cellular contractility is modified, and higher compressive forces rise from the confined growth of the tumor [28][29][30][31] . Furthermore, intercellular contact-induced arrest of cell growth and contact inhibition underlies the homeostatic control of cell growth, density and tissue/organ size 14,32 .…”

Section: Introductionmentioning

confidence: 99%

Brick Strex – A Robust Device Built of LEGO® Bricks for Mechanical Manipulation of Cells

Mäntylä

Ihalainen

2021

Preprint

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Cellular forces, mechanics and other physical factors are important co-regulators of normal cell and tissue physiology. These cues are often misregulated in diseases such as cancer, where altered tissue mechanics contribute to the disease progression. Furthermore, intercellular tensile and compressive force related signaling is highlighted in collective cell behavior during development. However, the mechanistic understanding on the role of physical forces in regulation of cellular physiology, including gene expression and signaling, is still lacking. This is partly because studies on the molecular mechanisms of force transmission require easily controllable experimental designs. These approaches should enable both easy mechanical manipulation of cells and, importantly, readouts ranging from microscopy imaging to biochemical assays. To achieve a robust solution for mechanical manipulation of cells, we developed devices built of LEGO® bricks allowing cell stretching and compression studies. By using these devices, we show that b-catenin responds differentially to epithelial monolayer stretching and compression, either localizing more to the cell nuclei or cell-cell junctions, respectively. In addition, we show that epithelial compression drives cytoplasmic retention and phosphorylation of transcription coregulator YAP1. We provide a complete part listing and video assembly instructions, allowing other researchers to build and use the devices in cellular mechanics -related studies.

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Control of cell colony growth by contact inhibition

Cited by 35 publications

References 73 publications

Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Size-dependent patterns of cell proliferation and migration in freely-expanding epithelia

Brick Strex: a robust device built of LEGO bricks for mechanical manipulation of cells

Brick Strex – A Robust Device Built of LEGO® Bricks for Mechanical Manipulation of Cells

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