Adhesion dynamics of circulating tumor cells under shear flow in a bio-functionalized microchannel

Abstract

The adhesion dynamics of circulating tumor cells in a bio-functionalized microchannel under hydrodynamic loading is explored experimentally and analyzed theoretically. EpCAM antibodies are immobilized on the microchannel surface to specifically capture EpCAM-expressing target breast cancer cells MDA-MB-231 from a homogeneous cell suspension in shear flow. In the cross-stream direction, gravity is the dominant physical mechanism resulting in continuous interaction between the EpCAM cell receptors and the immobilized surface anti-EpCAM ligands. Depending on the applied shear rate, three dynamic states have been characterized: firm adhesion, rolling adhesion and free rolling. The steady-state velocity under adhesion- and free-rolling conditions as well as the time-dependent velocity in firm adhesion has been characterized experimentally, based on video recordings of target cell motion in functionalized microchannels. A previously reported theoretical model, utilizing a linear spring to represent the specific receptor–ligand bonds, has been adopted to analyze adhesion dynamics including features such as the cell–surface binding force and separation gap. By fitting theoretical predictions to experimental measurements, a unified exponential decay function is proposed to describe the target cell velocity evolution during capture; the fitting parameters, velocity and time scales, depend on the particular cell–surface system.