Measure and characterization of the forces exerted by growing multicellular spheroids using microdevice arrays.

Growing multicellular spheroids recapitulate many features of expanding microtumours, and therefore they are an attractive system for biomechanical studies. Here, we report an original approach to measure and characterize the forces exerted by proliferating multicellular spheroids. As force sensors, we used high aspect ratio PDMS pillars arranged as a ring that supports a growing breast tumour cell spheroid.

Are Tumor Cell Lineages Solely Shaped by Mechanical Forces?

This paper investigates cell proliferation dynamics in small tumor cell aggregates using an individual-based model (IBM). The simulation model is designed to study the morphology of the cell population and of the cell lineages as well as the impact of the orientation of the division plane on this morphology. Our IBM model is based on the hypothesis that cells are incompressible objects that grow in size and divide once a threshold size is reached, and that newly born cell adhere to the existing cell cluster.

Imaging tissue-mimic with light sheet microscopy: A comparative guideline.

Tissue mimics (TMs) on the scale of several hundred microns provide a beneficial cell culture configuration for in vitro engineered tissue and are currently under the spotlight in tissue engineering and regenerative medicine. Due to the cell density and size, TMs are fairly inaccessible to optical observation and imaging within these samples remains challenging. Light Sheet Fluorescence Microscopy (LSFM)- an emerging and attractive technique for 3D optical sectioning of large samples- appears to be a particularly well-suited approach to deal with them.

Cell-Cell Adhesion and Cytoskeleton Tension Oppose Each Other in Regulating Tumor Cell Aggregation.

Cell aggregation is frequently impaired during the growth of primary tumors and the formation of metastatic lesions. Cell aggregation depends on cell-cell adhesion; however, no rigorous approach exists to monitor and quantify it accurately in the absence of the confounding factors of cell-substrate adhesion and the resulting cell motility on the substrate. We report here a highly reproducible, automated, microscopy-based quantification of tumor-cell spheroid formation in the absence of cell-substrate adhesion and use it to characterize cell aggregation dynamics in the early steps of this process.

Multicellular tumor spheroid models to explore cell cycle checkpoints in 3D.

Background: MultiCellular Tumor Spheroid (MCTS) mimics the organization of a tumor and is considered as an invaluable model to study cancer cell biology and to evaluate new antiproliferative drugs. Here we report how the characteristics of MCTS in association with new technological developments can be used to explore the regionalization and the activation of cell cycle checkpoints in 3D.

Methods: Cell cycle and proliferation parameters were investigated in Capan-2 spheroids by immunofluorescence staining, EdU incorporation and using cells engineered to express Fucci-red and -green reporters.