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.

Effects of flowing RBCs on adhesion of a circulating tumor cell in microvessels

“…In order to step out of the flow, a very important step is the so called “adhesion cascade” (Guo et al 2004; Haier and Nicolson 2001; Stroka and Konstantopoulos 2014; Wirtz et al 2011). Most previous studies have experimentally (Cheung et al 2011; Fu et al 2015; Guo et al 2014; Yan et al 2012; Zhang et al 2016) and numerically (Rejniak 2012; Yan et al 2012; Yan et al 2010) investigated the process of cell adhesion to the blood vessel. The numerical studies simply regarded the blood as a homogenous Newtonian fluid (Rejniak 2012; Yan et al 2010).…”

Isolation of viable cancer cells in antibody-functionalized microfluidic devices

“…Several studies on cell attachment and detachment have provided useful data on receptor-mediated adhesion kinetics. [15][16][17] The adhesion force is derived from the number and strength of bonds formed between the cell and the surface. The number of active bonds, contributing to the resultant adhesion force, depends on both membrane receptor and surface ligand densities.…”

“…In our previous work, we characterized the attachment and detachment of circulating tumor cells in antibody-functionalized microchannels, [15][16][17] and proposed a particular flow pattern to enhance the system performance in specifically isolating target cells. 33 We reported a characteristic shear rate controlling the fraction of cells captured under applied shear flow.…”

Flow-rate dependent capture of circulating tumor cells in bio-functional microchannels

“…Several studies on cell attachment and detachment have provided useful data on receptor-mediated adhesion kinetics [7,8]. The high-affinity, highly specific receptorligand binding is of considerable importance in medicine and biotechnology.…”

“…The governing equations of this highly non-linear phenomenon preclude close-form analytical solutions; however, based on experiments, mathematical models are proposed to quantitatively estimate the effect of various parameters. In our previous work, we characterized the attachment and detachment of circulating tumor cells in antibodyfunctionalized microchannels [7,8], and applied a particular flow pattern scheme to enhance the system performance in specifically isolating target cells [15]. We also explored the effects of cell receptor and surface ligand densities on cell capture under shear flow.…”