Impacts of Morphology and Elasticity on Cancer Cell Deformation in Shear Flows.

PURPOSE: This work investigates the role of morphology and elasticity on cancer cell deformation under shear flow in a microchannel. METHODS: A novel hybrid continuum-particle framework is developed to simulate cancer cell dynamics. Cell membrane and nucleus geometries are reconstructed from microscopic images and modeled using dissipative particle dynamics, while the surrounding blood plasma is treated as an incompressible Newtonian fluid. Cell-flow interactions are captured via an immersed boundary method. RESULTS: All cancer cell models exhibited a rapid deformation response within the first 1-2 ms, followed by morphology- and stiffness-dependent shape evolution. The compact morphologies showed strong recovery, whereas the other models evolved toward folded/lobed states with only intermittent partial recovery during shape transitions. Membrane stiffening dominated elongation and compactness loss, while nuclear stiffening modulated deformation excursions and partial recovery. These shape transitions were accompanied by near-field vortex reorganization and traction localization. Similar to deformation response, the net membrane force exhibited a common start-up rise within 0-0.5 ms followed by relaxation. Compact morphologies produce lower and steadier forces. They show minimal stiffness dependence. Deformation-prone morphologies show stronger unsteadiness and clearer stiffness modulation. Cross-sectional velocity and vorticity fields showed a dominant hydrodynamic imbalance and lateral migration. CONCLUSION: Our results demonstrate that morphology sets the stiffness-modulated deformation patterns which affects the extracellular flow dynamics and traction. In turn, the resulting flow field and traction distribution feedback to influence subsequent deformation and migration. This mechanistic link provides a framework for interpreting circulating tumor cell transport in shear-dominated metastatic environments.