Migration of circulating tumor cells through a heterogeneous constriction network

Metastasis represents one of cancer's most daunting challenges, responsible for a staggering 90% of cancer-related deaths. Although substantial progress has been made in cancer biology, the quantitative link connecting biological factors with the transport and deformation of CTCs (circulating tumor cells) within the complex vascular network remains elusive. We will present a microfluidic pore-network model designed to investigate the effects of heterogeneous constrictions on CTC migration, trapping, and death. The model introduces heterogeneity in constriction size based on a vascular capillary network, inducing a complex velocity field within the circulating fluid. High-speed fluorescence microscopy is employed to simultaneously measure fluid and CTC velocities, along with the trapping locations. To complement these experiments, we employ a phase-field modelling technique, to simulate the CTC migration in the heterogeneous pore-network. The local deformation, transport, and trapping of migrating cells are governed by the viscous stress field and the spatial distribution of pore sizes. Additionally, the inclusion of CTCs as a secondary phase, circulating and trapped within the heterogeneous porous system, alters the fluid velocity field, leading to a two-way coupling effect that further influences the medium's heterogeneity, porosity, and permeability. In this talk, we will present preliminary data showcasing the coupling effect between CTCs and the fluid flow, shedding light on the development of a statistical model to predict CTC breakthrough through the network. This research offers promising insights into the mechanics of metastasis and potential implications for devising novel therapeutic strategies.