ORION · HydrOdynamics & biomechanics of canceR cell mIgration in heterOgeNeous media

So far medicine has not solved the workings of a formidable and scientifically challenging aspect of cancer: metastasis, the migration of circulating tumor cells (CTC) through the body. In this highly interdisciplinary project, expertise and techniques from fluid dynamics are employed to study how CTC move through the vascular network and what prompts them to do so. The complex interplay among hydrodynamics, biophysics of intracellular interactions, and biochemical signaling within vascular networks is unknown. Our understanding of these underlying processes is hindered by the complex heterogeneity in the vascular network, comprising of capillaries, veins and arteries with a wide range of size and structural diversity. To unravel these processes I bring my expertise in fluid dynamics and porous media together with the state-of-the-art facilities on experimental cancer mechanobiology and multiscale modeling at the host and secondment institutes. I will conduct microfluidic experiments and simulations by simplifying the vascular network as strategically designed pore-network models. First, I will study the two-way interactions between the heterogeneous flow field and the deformable CTCs that control their overall transport, deformation and trapping. A heterogeneous flow field also induces a spatially nonuniform scalar concentration across the medium. CTCs are highly sensitive to certain biochemicals that can alter motility and invasiveness of CTCs. I will investigate how the local gradients of such biochemicals in a heterogeneous microsystem influence CTC migration. Finally, I will study the collective migration of CTC clusters through the system and quantify the dynamic intracellular interaction by measuring membrane tension and intracellular adhesion forces. These investigations will provide novel understandings on cancer metastasis that I will strategically communicate to research communities, stakeholders and general public.