A hybrid computational model of cancer spheroid growth with ribose-induced collagen stiffening

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

Опубликована: Окт. 27, 2024

Abstract Metastasis, the leading cause of death in cancer patients, arises when cells disseminate from a primary solid tumour to distant organs. Growth and invasion often involve collective cell migration, which is profoundly influenced by cell-cell interactions extracellular matrix (ECM). The ECM’s biochemical composition mechanical properties, such as stiffness, regulate behaviour migration dynamics. Mathematical modelling serves pivotal tool for studying predicting these complex dynamics, with hybrid discrete-continuous models offering powerful approach combining agent-based representations continuum descriptions surrounding microenvironment. In this study, we investigate impact ECM modulated via ribose-induced collagen cross-linking, on spheroid growth invasion. We employed model implemented PhysiCell simulate successfully replicating three-dimensional vitro experiments. incorporates detailed cell-ECM interactions, remodelling, proliferation. Our simulations align experimental observations two breast lines, non-invasive MCF7 invasive HCC1954, under varying stiffness conditions. results demonstrate that increased due cross-linking inhibits cells, whereas remain largely unaffected. Furthermore, our show higher degradation not only enables but also facilitates formation multicellular protrusions. Conversely, increasing maximum speed can reach enhances while promoting single-cell This understanding interplay between proliferation, paving way future studies incorporating additional characteristics microenvironmental

Язык: Английский

---

Filopodia: integrating cellular functions with theoretical models

Trends in Cell Biology, Год журнала: 2024, Номер unknown

Опубликована: Июль 1, 2024

Язык: Английский

---

A multiparametric analysis including single-cell and subcellular feature assessment reveals differential behavior of spheroid cultures on distinct ultra-low attachment plate types

Frontiers in Bioengineering and Biotechnology, Год журнала: 2024, Номер 12

Опубликована: Авг. 2, 2024

Spheroids have become principal three-dimensional models to study cancer, developmental processes, and drug efficacy. Single-cell analysis techniques emerged as ideal tools gauge the complexity of cellular responses in these models. However, single-cell quantitative assessment based on 3D-microscopic data subcellular distribution fluorescence markers, such nuclear/cytoplasm ratio transcription factors, has largely remained elusive. For spheroid generation, ultra-low attachment plates are noteworthy due their simplicity, compatibility with automation, experimental commercial accessibility. it is unknown whether what degree plate type impacts formation biology. This developed a novel AI-based pipeline for 3D-confocal optically cleared large spheroids at wholemount, single-cell, sub-cellular levels. To identify relevant samples pipeline, automated brightfield microscopy was employed systematically compare size eccentricity formed six different types using four distinct human cell lines. showed that all exhibited similar spheroid-forming capabilities gross patterns growth or shrinkage during 4 days after seeding were comparable. Yet, varied among specific lines types. Based this prescreen, HaCaT keratinocytes HT-29 cancer cells further assessed. In spheroids, in-depth revealed correlation between size, proliferation, transcriptional coactivator, YAP1, well an inverse respect differentiation. These findings, yielded model level, corroborate earlier concepts role YAP1 proliferation differentiation skin. Further, results show may influence outcome campaigns advisable scan optimal configuration investigation.

Язык: Английский

---

Agent-based modeling reveals impacts of cell adhesion and matrix remodeling on cancer collective cell migration phenotypes

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

Опубликована: Дек. 23, 2024

Abstract Understanding the phenotypic transitions of cancer cells is crucial for elucidating tumor progression mechanisms, particularly transition from a non-invasive spheroid phenotype to an invasive network phenotype. We developed agent-based model (ABM) using Compucell3D, open-source biological simulation software, investigate how varying biophysical and biochemical parameters influence emerging properties cellular communities, including cell growth, division, migration. Our focus was on cell-cell contact adhesion matrix remodeling effects simplified enzymatic extracellular subsequent enhancements chemotaxis or durotaxis as combined effect localized secretion chemoattractant. By chemoattractant rate energy, we simulated their behavior driving The serves digital twin 3D culture, simulating invasion over 1 week, validated against published data. simulations track emergent morphological collective changes key metrics such circularity invasion. findings indicate that increased enhances invasiveness cells, promoting Additionally, changing energy strong weak affects compactness spheroids, resulting in lower work advances understanding by providing insights into mechanisms behind transitions.

Язык: Английский

---