Multiscale modelling of sarcoma and bone tissue synergy and interactions

National audienceBone sarcomas are extremely invasive tumours, at the expense of patients prognosis. Precision of ablation of pathological tissue during surgical treatment can largely be improved and novel signalling pathways targeted by poly-chemotherapy must be discovered. The purpose of my project is to explore fundamental mechanisms underlying bone and Ewing sarcomas aggressiveness by means of computer-based simulations at the tissue and molecular scales. We have recently hypothesised that sarcomas proliferation results from the double catalysis of sarcomas by bone tissue and bone tissue by sarcomas. The spectacular morphology of the remodelled bone tissue in presence of tumour cells may well be induced by this synergetic effect triggered by signalling molecules released by sarcomas. We have developed a simple model based on a cellular automaton of the evolution of bone tissue and sarcoma morphology accounting for both catalytic effects. Simulations results show the dependence of the morphology to the double catalysis. This demonstration orients our recent research toward clarifying the specific molecular signals capable of triggering this synergetic mechanism. To that extent, I am now pursuing our investigations at the molecular scale by investigating the mechanisms of mineralisation of collagen fibrils altered by such potential molecular signalling. I perform molecular dynamics simulations of the hydration of collagen microfibrils to determine how mineral transport and deposition occurs. These simulations will help us understand in detail the catalytic effect of sarcoma on bone tissue remodelling, and in particular why its results in weakly mineralised collagen structures similar to osteid