Controlling cellular packing and hypoxia in 3D tumor spheroids via DNA interactions DOI Creative Commons

Sven A. Saemundsson,

Shane D. Curry,

Bryce M. Bower

и другие.

Biomaterials Science, Год журнала: 2024, Номер 12(18), С. 4759 - 4769

Опубликована: Янв. 1, 2024

Tumor spheroids represent valuable in vitro models for studying cancer biology and evaluating therapeutic strategies. In this study, we investigated the impact of varying lengths DNA-modified cell surfaces on spheroid formation, cellular adhesion molecule expression, hypoxia levels within 4T1 mouse breast spheroids. Through a series experiments, demonstrated that modifying with biotinylated DNA strands different facilitated formation without significantly altering expression fibronectin e-cadherin, key molecules. However, our findings revealed notable influence length As increased, decreased, indicating enhanced intercellular spacing porosity structure. These results contribute to better understanding how modification can modulate architecture microenvironmental conditions. Such insights may have implications developing interventions targeting tumor microenvironment improve treatment efficacy.

Язык: Английский

Mechanical signatures in cancer metastasis DOI Creative Commons
Ayushi Agrawal,

Yousef Javanmardi,

Sara A. Watson

и другие.

npj Biological Physics and Mechanics., Год журнала: 2025, Номер 2(1)

Опубликована: Фев. 4, 2025

Abstract The cancer metastatic cascade includes a series of mechanical barrier-crossing events, involving the physical movement cells from their primary location to distant organ. This review describes changes that influence tumour proliferation, progression, and metastasis. We identify potential signatures at every step discuss some latest mechanobiology-based therapeutic interventions highlight importance interdisciplinary approaches in diagnosis treatment.

Язык: Английский

Процитировано

2
Patient Specific Colorectal Cancer-Associated Fibroblasts Modulate Tumour Microenvironment Mechanics DOI Creative Commons
Auxtine Micalet,

Anuja Upadhyay,

Yousef Javanmardi

и другие.

iScience, Год журнала: 2024, Номер 27(6), С. 110060 - 110060

Опубликована: Май 21, 2024

Highlights•Patient-specific CAFs exhibited heterogeneity in tissue remodeling capabilities•Tissue stiffening was mainly attributed to the contraction of matrix by cells•Tissue softening due enzymatic activity matrix-cleaving proteins•Interplay between cancer cells and critical as it stopped heterogeneitySummaryCancer-associated fibroblasts (CAFs) play a major role reorganizing physical tumor micro-environment changing stiffness. Herein, using an engineered three-dimensional (3D) model that mimics tumor's native biomechanical environment, we characterized changes stiffness caused six patient-specific colorectal CAF populations. After 21 days culture, atomic force microscopy (AFM) performed precisely measure local Each population capabilities, with some patient-derived others it. Tissue active cells, whereas proteins. This measured lost when were cocultured all samples significantly soften tissue. The interplay altered any alone.Graphical abstract

Язык: Английский

Процитировано

5
Quantitative characterization of the 3D self-organization of PDAC tumor spheroids reveals cell type and matrix dependence through advanced microscopy analysis DOI Creative Commons
Soraya Hernández-Hatibi, Carlos Borau, Neus Martínez‐Bosch

и другие.

APL Bioengineering, Год журнала: 2025, Номер 9(1)

Опубликована: Март 1, 2025

Pancreatic ductal adenocarcinoma (PDAC) is characterized by an abundant tumor-associated stroma composed from pancreatic stellate cells, which play a critical role in tumor progression. Developing accurate vitro models requires understanding the complex interactions between cells and their microenvironment. In this study, we present quantitative imaging-based characterization of three dimensional (3D) self-organization PDAC tumour spheroids using microfluidic platform that mimics key aspects Our model incorporates collagen type I hydrogels to recreate extracellular matrix, activated human (HPSCs), various cell types. Advanced imaging techniques, including Lattice Lightsheet Microscopy, allowed us analyze 3D growth spatial organization spheroids, revealing intricate biomechanical interactions. results indicate alterations matrix properties-such as stiffness, pore size, hydraulic permeability-due variations concentration significantly influence patterns depending on subtype epithelial-mesenchymal phenotype. Higher concentrations promoted larger epithelial-like lines, while mesenchymal-type required increased for into smaller spheroids. Furthermore, coculture with HPSCs affected spheroid formation distinctly based each line's genetic phenotypic traits. had opposing effects lines: one line exhibited enhanced growth, another showed inhibited formation, whereas mesenchymal-like minimal impact. These provide insights tumor-stroma interactions, emphasizing importance cell-specific matrix-dependent factors advancing our progression informing future therapeutic strategies.

Язык: Английский

Процитировано

0
Automated Quality Control of Time-Course Imaging from 3D in vitro cultures DOI Creative Commons
Eric Cramer, Tamara Y. Lopez-Vidal, Jeanette Johnson

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 5, 2025

Longitudinal imaging of 3D cell cultures like tumor organoids and spheroids offers crucial insights into cancer progression treatment. However, spatial displacement during time-course imaging, caused by matrix detachment or experimental artifacts, can confound analyses. Existing computational methods struggle to address this issue. We present a new algorithm evaluate data integrity rectify mislabeling in longitudinal culture. Our integrates permutation-based optimization with Procrustes analysis. By using X Y coordinates images, it accurately reorders, matches, aligns object positions across time points, correcting for rotation, translation, small movements. Validation simulated confirmed its accuracy robustness. Applied spheroids, our revealed frequent amongst the between points corrected many mislabeled images. This computationally efficient adaptable method needs no adjustments presents readily accessible solution quality control. Three-dimensional (3D) vitro models, such as embedded an extracellular matrix, are increasingly vital studying normal disease biology, including drug responses. 1-3 A key advantage these models is that platforms perform continuous track phenotypic changes. common issues techniques, shifts setup image capture, introduce technical artifacts affect downstream Currently, automated analytical approaches exist assessing artifacts. Here, we robust, and, some cases, enable accurate tracking individual over time. approach relies only on metadata, requiring modifications. It implementable improving reproducibility enhancing reliability culture studies.

Язык: Английский

Процитировано

0
Multicellular tumor spheroids: A convenient in vitro model for translational cancer research DOI
Tushar Patel, Neeraj Jain

Life Sciences, Год журнала: 2024, Номер 358, С. 123184 - 123184

Опубликована: Окт. 28, 2024

Язык: Английский

Процитировано

3
Regularization techniques and inverse approaches in 3D Traction Force Microscopy DOI Creative Commons
Alejandro Apolinar–Fernández, Pablo Blázquez-Carmona, Raquel Ruiz-Mateos

и другие.

International Journal of Mechanical Sciences, Год журнала: 2024, Номер 283, С. 109592 - 109592

Опубликована: Июль 30, 2024

The conception of inverse methods in the context Traction Force Microscopy (TFM) is influenced by multiple factors, such as nonlinear effects, dimensionality (2D/3D), and regularization/constraints, amongst others. Solving problem often requires inversion a matrix, presence noise measured displacements can lead to unrealistic reconstructed tractions. To address this issue, Tikhonov regularization commonly used, penalizing high norm values computed aim study compare performance different methodologies (including some original variations) 3D TFM, considering constraint imposition along formulation. are numerically elaborated within novel combined Newton–Raphson/Finite Element Method scheme that provides converged solutions few iterations. impact traction reconstruction evaluated terms accuracy, efficiency (CPU time), inherent characteristics methodology. Results show that, applying constraints (based on fulfillment fundamental principles) best reconstruction, while simultaneously ensuring an optimum estimate maximum traction, at cost CPU time low efficiency. Moreover, regularization-based introduce challenge calibrating parameter, usually done under subjective criteria. On other hand, non-regularized but constrained may represent nice compromise between accuracy efficiency, avoiding pre-processing calibration parameter. It emphasized importance not only quality also complexity implementation (intrusiveness) when selecting appropriate method for TFM analysis.

Язык: Английский

Процитировано

1
Controlling cellular packing and hypoxia in 3D tumor spheroids via DNA interactions DOI Creative Commons

Sven A. Saemundsson,

Shane D. Curry,

Bryce M. Bower

и другие.

Biomaterials Science, Год журнала: 2024, Номер 12(18), С. 4759 - 4769

Опубликована: Янв. 1, 2024

Tumor spheroids represent valuable in vitro models for studying cancer biology and evaluating therapeutic strategies. In this study, we investigated the impact of varying lengths DNA-modified cell surfaces on spheroid formation, cellular adhesion molecule expression, hypoxia levels within 4T1 mouse breast spheroids. Through a series experiments, demonstrated that modifying with biotinylated DNA strands different facilitated formation without significantly altering expression fibronectin e-cadherin, key molecules. However, our findings revealed notable influence length As increased, decreased, indicating enhanced intercellular spacing porosity structure. These results contribute to better understanding how modification can modulate architecture microenvironmental conditions. Such insights may have implications developing interventions targeting tumor microenvironment improve treatment efficacy.

Язык: Английский

Процитировано

1