Biomedical Engineering Seminar: Systems Biology of drug response and metastasis through multi-scale modeling, novel biomaterials and high-throughput imaging
Building 193, Electrical and Electronic Engineering Building
T: (03) 8344 6606
Cancer cell migration, signaling and response to therapeutics have historically been carried out in two-dimensional environments that are far from in vivo. These environments create artificial polarities, mediate unrealistic cell-matrix interactions and lead to signaling cascades that paint an incomplete and inaccurate picture of cancer cell behavior in vivo. Consequently, our understanding of matrix mechanical regulation of therapeutic efficacy and chemoresistance is qualitative and fragmented. Additionally, current computational models are unable to connect biochemical signaling events at the molecular level with biomechanical processes observed in native like 3D environments making the predictive power of models limited in their scope.
Using a combination of multi-scale modeling approaches (deterministic, finite element, molecular simulations) with development and application of novel synthetic and naturally occurring matrices and high resolution imaging we quantitatively investigate single and collective cell behavior of metastatic breast cancer cells and analyze the response of adhesion, kinase, apoptosis and proliferation pathways in a number of complex native environments. Our results indicate the presence of multiple novel biomechanical signaling pathways in regulating cellular fate in 3D that have not been observed in 2D environments. Overall, our results not only provide a scalable platform for detailed cellular investigation but also demonstrate how breast tumor cells, in isolation or as a collective, develop chemoresistance as a function of the matrix mechano-chemical environment, therefore identifying new pathways for therapeutic intervention.