ECM stiffness effects and subtumor formation in glioma growth. In Silico model

Vladimir Kalinin^1
1R&D section, TMA, Dundalk, Ireland, vladimir.kalinin@tma-science.ie

This study is based on in silico model and demonstrates how variations of Extracellular Matrix (ECM) stiffness may affect glioma invasive scenarios. The model describes cell proliferation and transport through elastic and compressible cell- ECM composite, including “go/grow” transitions determined by oxygen concentrations.  Simulations generate invasive scenarios conditioned only by set of mechanical characteristics of cell-ECM composite typical for gliomas. Multicellular Tumor Spheroid (MTS) growing in soft matrix exhibits gentle cell density profile with elongated low density invasive zone, while rigid ECM conditions sharp edge of MTS and higher invasion speed. Moreover, the highest speed of tumor invasion is obtained at intermediate values of ECM stiffness, when a compact cell cluster is being formed instead of invasive zone as a second proliferative layer out of the core spheroid.