Quantitative characterization of viscoelastic fracture induced by time-dependent intratumoral pressure in a 3D model tumor.

In the tumor environment, interstitial pressure drives interstitial flow drainage from the tumor core to the lymphatic vessels. Recent studies have highlighted the key role of interstitial pressure in tumor development and cell migration. High intratumoral pressures, up to 60 mm Hg , have been reported in cancer patients. In a previous study, we showed that such pressure levels induce fracture in an experimental tumor model consisting of a microfluidic system holding a cellular aggregate. Here, we investigate and quantify the characteristics of tumor model fracture under a range of flow conditions. Our findings suggest a strong dependence of viscoelastic fracture behavior on the loading rate exerted by flow. The aggregate exhibits fragile fracture at high loading rates and ductile fracture at lower rates. The loading rate also modifies the permeability of the cellular aggregate, as well as the persistence time of the load required to induce fracture. The quantification parameters we propose here, evaluated for an in vitro model tumor without the extracellular matrix, could be applied to characterize tumor fracture under more realistic interstitial flow conditions.