Biomechanics of 3D tumor cell cultures of human breast carcinoma cells (T47D)

Multicell tumor spheroids are three-dimensional cultures of tumor cells. The idea of
reconstituting 3D aggregates of cells in vitro as experimental models of real tissues dates
back to the first half of the 20th century. Indeed the 3D dimensional architecture promotes deep molecular and metabolic changes to cells and thus to their microenvironment . These changes – just to cite a few of the most important aspects – affect the sensitivity of cells to anti-tumor therapies and determine the onset of new malignant phenotypes such as the acquired ability of the cells to migrate and invade surrounding environments. In spite of obvious limitations – for example spheroids lack a vascular network – traditional
tumor spheroids are still considered a good experimental model of human solid tumors.
When solid tumors grow in vivo they exert a finite force on the surrounding tissue that results in the generation of solid stress. Theoretical and experimental works suggested that cell aggregates can be more appropriately represented as space-filling assemblies of deformable cells. Thus spheroids would be more similar to materials such as liquid foams. However, alive cells are not just passive structures subjected to physical forces. Oral squamous carcinoma spheroids grown in engineered culture environments with different stiffness clearly showed that the cells sense mechanical stimuli and react to them by reprogramming the expression of a variety of genes. Stiff matrices induced the upregulation of genes associated to mechanotransduction, ion channel transport, extracellular matrix remodeling, tumorigenesis, cell adhesion. Importantly, these biochemical pathways are related to cell metabolism. Some of the protein involved rely directly on energy availability under the form of adenosine triphosphate (ATP), such as e.g. ATP-dependent ion transporters, but more generally signal transduction biochemical pathways act through the phosphorylation/de-phosphorylation of specific protein nodes and thus they are dependent upon the intracellular concentration of ATP. Thus, the response of spheroids to mechanical stress might be more complex than that shown by liquid foams.
The main goal of this research project is the quantification of the metabolic status of tumor spheroids subjected to mechanical stress. To this purpose, a micro-scale uniaxial tension-compression test system was used. Two mechanical parameters were measured in these experiments, namely the maximum measured force F_{max} and the area of the hysteresis loop A_h that is clearly visible in force/deformation plots. A_h is a measure of the energy dissipated by the spheroids during the stress tests and wether this energy could be related to ATP consumption by spheroids was the starting hypothesis of the present analysis.
Here, the experimental data collected for spheroids individually subjected to mechanical load are made available to the scientific community.