SimuCell3D: three-dimensional simulation of tissue mechanics with cell polarization

Nature Computational Science, Год журнала: 2024, Номер 4(4), С. 299 - 309

Опубликована: Апрель 9, 2024

Abstract The three-dimensional (3D) organization of cells determines tissue function and integrity, changes markedly in development disease. Cell-based simulations have long been used to define the underlying mechanical principles. However, high computational costs so far limited either simplified cell geometries or small patches. Here, we present SimuCell3D, an efficient open-source program simulate large tissues three dimensions with subcellular resolution, growth, proliferation, extracellular matrix, fluid cavities, nuclei non-uniform properties, as found polarized epithelia. Spheroids, vesicles, sheets, tubes other can readily be imported from microscopy images simulated infer biomechanical parameters. Doing so, show that 3D shapes layered pseudostratified epithelia are largely governed by a competition between surface tension intercellular adhesion. SimuCell3D enables large-scale silico study disease at great level detail.

Язык: Английский

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Organoids in high-throughput and high-content screenings

Frontiers in Chemical Engineering, Год журнала: 2023, Номер 5

Опубликована: Март 21, 2023

Organoids are self-organized three-dimensional (3D) multicellular tissue cultures which derive from cancerous and healthy stem cells, sharing a highly similarity to the corresponding in vivo organs. Since their introduction 2009, they have emerged as valuable model for studying early embryogenesis, organ development, well tools drug screening, disease modeling personalized therapy. can now be established various tissues, including brain, retina, thyroid, gastrointestinal, lung, liver, pancreas, kidney. These micro-tissues resemble native terms of gene expression, protein architecture cell-cell interactions. Despite success organoid-based research advances patient-derived organoid culture, important challenges remain. In this review, we briefly showcase evolution primary 3D systems complex, multilayered structures such assembloids, gastruloids ETiX embryoids. We discuss current developments highlight culturing analysis make organoids accessible high-throughput high-content screening. Finally, summarize potential machine learning computational conjunction with systems.

Язык: Английский

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PolyHoop: Soft particle and tissue dynamics with topological transitions

Computer Physics Communications, Год журнала: 2024, Номер 299, С. 109128 - 109128

Опубликована: Фев. 15, 2024

We present PolyHoop, a lightweight standalone C++ implementation of mechanical model to simulate the dynamics soft particles and cellular tissues in two dimensions. With only few geometrical physical parameters, PolyHoop is capable simulating wide range particulate matter systems: from biological cells vesicles, bubbles, foams, emulsions, other amorphous materials. The or are represented by continuously remodeling, non-convex, high-resolution polygons that can undergo growth, division, fusion, aggregation, separation. tissue foam consisting million with high spatial resolution be simulated on conventional laptop computers. Program Title: CPC Library link program files: https://doi.org/10.17632/4jscxhkd2s.1 Licensing provisions: BSD 3-clause Programming language: C++11 Supplementary material: Figures ?? ??, Movies 1–7 Nature problem: Various two-dimensional systems elastic, tensile hoops marking boundaries fluidic domains. Examples include tissues, etc. efficiently solves Newtonian such systems, enabling simulation large ensembles O(106) deformable single ordinary CPU. variety topological transitions as division fusion. Solution method: their boundary contours, discretized into polygons. polygon vertices then propagated time solving Newtons's equation motion semi-implicit Euler method, using conservative dissipative nodal forces. To maintain quality discretization even during particle deformations, automatically remodel boundaries. For efficient collision detection, partitioning grid used. Additional comments including restrictions unusual features: source code exceptionally compact, about 720 commented lines file. no dependencies, it highly portable easy handle, making also suited for educational purposes.

Язык: Английский

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Polarity-driven three-dimensional spontaneous rotation of a cell doublet

Nature Physics, Год журнала: 2024, Номер 20(7), С. 1194 - 1203

Опубликована: Май 13, 2024

Abstract Mechanical interactions between cells play a fundamental role in the self-organization of organisms. How these drive coordinated cell movement three dimensions remains unclear. Here we report that doublets embedded three-dimensional extracellular matrix undergo spontaneous rotations. We investigate rotation mechanism and find it is driven by polarized distribution myosin within cortices. The mismatched orientation this breaks doublet mirror symmetry. In addition, adhere at their interface through adherens junctions with focal contacts near clusters. use physical theory describing as two interacting active surfaces to show myosin-generated gradients tension whose profiles are dictated polarity axes. also shape symmetries related broken To test for mechanism, suppress clusters using laser ablation generate new optogenetics. Our work clarifies how polarity-oriented mechanical forces collective motion dimensions.

Язык: Английский

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Strain softening and hysteresis arising from 3D multicellular dynamics during long-term large deformation

Journal of the mechanical behavior of biomedical materials/Journal of mechanical behavior of biomedical materials, Год журнала: 2025, Номер unknown, С. 107001 - 107001

Опубликована: Апрель 1, 2025

Язык: Английский

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Vertex models capturing subcellular scales in epithelial tissues

PLoS Computational Biology, Год журнала: 2025, Номер 21(5), С. e1012993 - e1012993

Опубликована: Май 21, 2025

Vertex models provide a robust theoretical framework for studying epithelial tissues as network of cell boundaries. They have been pivotal in exploring properties such packing geometry and rigidity transitions. Recently, extended vertex become instrumental bridging the subcellular scales to tissue scale. Here, we review extensions model aiming capture experimentally observed features including heterogeneity myosin activity across tissue, non-uniform contractility structures, mechanosensitive feedback loops. We discuss how these change challenge current perspectives on observables macroscopic properties. First, find that can significantly, impacting critical threshold some cases even existence transition. Second, disorder be explained by employing different mechanisms, indicating source stochasticity gradual local size changes common mesoscopic motifs mechanics organization. address complementary statistical inference, putting broader methodological context give brief overview software packages utilized increasingly complex studies. Our emphasizes need more comparative, systematic studies identify specific classes which share set well-defined properties, well in-depth discussion modeling choices their biological motivations.

Язык: Английский

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Dissecting the subcellular forces sculpting earlyC. elegansembryos

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Март 9, 2023

Summary Embryo shape is determined by individual cell mechanics, intercellular interaction strength, and geometrical constraints. Models based on surface tensions at interfaces can predict 3D static cellular arrangements within aggregates. However, predicting the dynamics of such challenging due to difficulties in measuring temporal changes tensions. Here, we characterise spatiotemporal shaping early nematode embryo using AFM, live microscopy, tension inference. Using excoriated embryos, validate a hybrid inference pipeline that calibrates relative inferred temporally cortical myosin enrichment absolute AFM measurements. Applied embryos their native shell, infer map tensions, revealing ABa, ABp, EMS compaction driven increased free surfaces, while P 2 ’s initial exclusion high contacts. We uncover direct non-affine contribution cadherins cell-cell contact tension, comparable cadherins’ indirect via actomyosin regulation. Highlights lineage cells have lower than AB Enrichment Myosin-II cortex good predictor cell-medium but not sufficient determine Myosin-informed allows determination evolution all embryo. compact compared interfaces, initially excluded Cadherins contribute directly non-linear way reducing nearly 50%. Open Access For purpose Access, author has applied CC BY public copyright license any Author Accepted Manuscript version arising from this submission.

Язык: Английский

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Modelling contractile ring formation and division to daughter cells for simulating proliferative multicellular dynamics

The European Physical Journal E, Год журнала: 2023, Номер 46(7)

Опубликована: Июль 1, 2023

Язык: Английский

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Predicting organoid morphology through a phase field model: insights into cell division and lumenal pressure

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Апрель 26, 2024

Abstract Organoids are ideal systems to predict the phenotypes of organs. However, there is currently a lack understanding regarding generalized rules that enable use simple cellular principles make morphological predictions entire organoids. Therefore, we employed phase field model with following basic components: minimum conditions for timing and volume cell division, lumen nucleation rules, lumenal pressure. Through our model, could compute generate myriad organoid observed till date. We propose indices necessary characterize shapes construct diagrams show their dependencies on proliferation time Additionally, introduced lumen-index parameter, which helped in examining criteria maintain organoids as spherical structures comprising single layer cells enclosing an intact lumen. Finally, star-like phenotype did not undergo differentiation, suggesting constraint during division may determine final phenotype. In summary, approach provides researchers guidelines test mechanisms self-organization shape organoid. Author summary nature, wide variety organ morphologies observed. Owing complexity process underlying acquisition organs’ morphology, it challenging investigate lead such variations. A promising study these variations “computational organoid” study, computational-based self-organizing multicellular assemblies fluid-filled cavities called lumens develop from few proliferating cells. This explores general dictate how various mechanical factors affect growing self-organized assembly. relied computer simulations mathematical phase-field explored factor effects, pressure while considering required division. These generated categorized range based varying conditions. were characterized into seven distinct classes, index sets, including monolayer/multilayer surrounding or multiple branch formation. obtained without assumption differentiation. Our elucidates formation different shapes, thereby highlighting significance forces shaping complex biological structures.

Язык: Английский

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Evolvoid: A genetic algorithm for shaping optimal cellular constructs

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Сен. 26, 2024

Abstract We describe an in-silico pipeline, Evolvoid, based on Genetic Algorithms (GAs) for identifying the optimal morphologies of cell-laden constructs. Driven by ad hoc selection rule (i.e., so-called fitness function (FF)), Evolvoid iteratively identifies characteristics genome) ‘survival fittest’ individual a given population throughout generations. The FF is universally observed biophysical laws, representing trade-off between i) high cell viability and robustness to changes in environmental oxygen ii) low surface energy. Shannon entropy used evaluate genome complexity, with most complex fittest individuals showing quantitative qualitative biological resemblance vitro paves way development “ lab laptop ”: high-fidelity cost-effective digital twins cellular constructs which could augment or even substitute costly models.

Язык: Английский

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