Physical basis for the determination of lumen shape in a simple epithelium

Vasquez, Claudia G.; Vachharajani, Vipul T.; Garzón-Coral, Carlos; Dunn, Alexander R.

doi:10.1038/s41467-021-25050-3

Cited by 31 publications

(27 citation statements)

References 57 publications

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“…It is difficult to speculate what mechanisms might govern this age-dependent quantitative change in constraints without perturbations. However, given that very young cysts seem to obey an entirely different set of constraints than older cysts, it may be that some of these differences are due to the establishment of apico-basal polarity around the lumen considering the work of Vasquez et al (Vasquez et al 2021). Also, we noticed in young cysts that the threshold of size and number of nuclei in order to form a lumen was 10,000 µm 3 and 7 nuclei, respectively (Supp.…”

Section: Resultsmentioning

confidence: 99%

Systematically quantifying morphological features reveals constraints on organoid phenotypes

Beck

Lee

Coté

et al. 2021

Preprint

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Organoids recapitulate complex 3D organ structures and represent a unique opportunity to probe the principles of self-organization. While we can alter an organoid’s morphology by manipulating the culture conditions, the morphology of an organoid often resembles that of its original organ, suggesting that organoid morphologies are governed by a set of tissue-specific constraints. Here, we establish a framework to identify constraints on an organoid’s morphological features by quantifying them from microscopy images of organoids exposed to a range of perturbations. We apply this framework to Madin-Darby Canine Kidney cysts and show that they obey a number of constraints taking the form of scaling relationships or caps on certain parameters. For example, we found that the number, but not size, of cells increases with increasing cyst size. We also find that these constraints vary with cyst age and can be altered by varying the culture conditions. This quantitative framework for identifying constraints on organoid morphologies may inform future efforts to engineer organoids.

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Section: Resultsmentioning

confidence: 99%

Systematically quantifying morphological features reveals constraints on organoid phenotypes

Beck

Lee

Coté

et al. 2021

Preprint

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“…The MDCK cell line retains the common physiological features of normal canine renal epithelial cells, including cell morphology, cell function and cell society [ 31 , 33 ]. In fact, this cell line has contributed to the elucidation of general biological phenomena such as cell–cell interactions and cell polarity in mammalian epithelial cells as well as renal epithelial cell functions [ 31 , 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…The cell line was established by Madin and Darby in 1958 from the kidney of a normal cocker spaniel [ 8 ]. This cell line was initially used in viral research but has since been used in basic biological epithelial cell research, including lumen formation, cell polarization, and cell differentiation, and in applied research including drug discovery and toxicology [ 31 , 32 , 33 , 35 ].…”

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confidence: 99%

Combined ataxia telangiectasia mutated and DNA-dependent protein kinase inhibition radiosensitizes Madin–Darby canine kidney cells

Koike

Yutoku

Koike

2022

The Journal of Veterinary Medical Science

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Uncovering radiation toxicity is critical for the adaptation and expansion of advanced radiation therapies and for the development of novel cancer radiotherapy. In the near future, advanced radiotherapies, including heavy ion beam treatment, are expected to be applied in the treatment of dogs, but further basic research on the effects of radiation using canine normal and cancer cells is necessary to actually apply these techniques and achieve high therapeutic efficacy. The radiation sensitivity is varied by the activities of DNA damage response (DDR) and DNA repair. The development of radiosensitizers that target DDR-and DNA repair-kinases, like ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PK), is progressing and is expected to be introduced into canine radiotherapy. However, there are no cytotoxicity reports on using the combination of radiation and these sensitizers as treatment in canine cells. In this study, we examined the cytotoxic effects of X-rays and/or radiosensitizers on the Madin-Darby Canine Kidney (MDCK) cell line. Our results show that X-rays suppress MDCK cell colony formation and proliferation in a dose-dependent manner. Additionally, our observations imply that the combination treatment with ATM inhibitor KU-55933 and DNA-PK inhibitor NU7441 significantly increased X-ray cytotoxicity in MDCK cells compared with the drugs alone. Furthermore, our findings further suggest that MDCK cells might be useful in clarifying the cytotoxicity in canine epithelial cells due to radiation and/or radiosensitizers, such as molecule-targeted drugs.

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“…Yet others, like the developing otic vesicle or the early drosophila embryo, are ellipsoidal 5,6 . In general, epithelia display a combination of shapes and a broad diversity of sizes, with lumens ranging from a few microns to several millimeters [7][8][9] . These diverse geometries enable optimal physiological processes and influence cellular fate and function [10][11][12][13] .…”

Section: Introductionmentioning

confidence: 99%

Mapping mechanical stress in curved epithelia of designed size and shape

Marín-Llauradó

Kale

Ouzeri

et al. 2022

Preprint

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The function of organs such as lungs, kidneys and mammary glands relies on the three-dimensional geometry of their epithelium. To adopt shapes such as spheres, tubes and ellipsoids, epithelia generate mechanical stresses that are generally unknown. Here we engineered curved epithelial monolayers of controlled size and shape and mapped their state of stress. We designed pressurized epithelia with circular, rectangular and ellipsoidal footprints. We developed a computational method to map the stress tensor in these epithelia. This method establishes a direct correspondence between epithelial shape and mechanical stress without assumptions of material properties. In epithelia with spherical geometry spanning more than one order of magnitude in radius, we show that stress weakly increases with areal strain in a size-independent manner. In epithelia with rectangular and ellipsoidal cross-section we found pronounced stress anisotropies consistent with the asymmetric distribution of tractions measured at the cell-substrate contact line. In these anisotropic profiles, cell shape tended to align with the direction of maximum principal stress but this alignment was non-universal and depended on epithelial geometry. Besides interrogating the fundamental mechanics of epithelia over a broad range of sizes and shapes, our approach will enable a systematic study of how geometry and stress influence epithelial fate and function in three-dimensions.

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Physical basis for the determination of lumen shape in a simple epithelium

Cited by 31 publications

References 57 publications

Systematically quantifying morphological features reveals constraints on organoid phenotypes

Systematically quantifying morphological features reveals constraints on organoid phenotypes

Combined ataxia telangiectasia mutated and DNA-dependent protein kinase inhibition radiosensitizes Madin–Darby canine kidney cells

Mapping mechanical stress in curved epithelia of designed size and shape

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