Energy consumption and biophysical response of 3D tumor cell cultures of human breast carcinoma cells (T47D) subjected to mechanical stress

Three-dimensional cultures of tumor cells (tumor spheroids) have long been used as an experimental model of solid tumors. Here, a uniaxial compression system has been used to mechanically perturb individual tumor spheroids. It was found that spheroids can consume up to 47% of their energy stores in the form of adenosine triphosphate when subjected to large mechanical loads, and that the maximum measured force decreases with the square root of the inverse strain rate. Both the compression phase and the relaxation of the force at constant strain were dependent upon the strain rate used to initially deform the spheroids. During the compression phase, a switch between a linear response (at strain rates below 0.002 s−1) and a nonlinear response (at higher strain rates) to deformation was observed. When the strain was held constant, force relaxation could be observed for spheroids initially deformed at high strain rates only. Overall, the observations suggest that tumor spheroids respond macroscopically to mechanical stress as shear-thinning fluids, a behavior that is likely to emerge at the population level as the result of energy-consuming pathways that individual cells activate to adapt to mechanical load.