Cell rolling and adhesion on surfaces in shear flow. A model for an antibody-based microfluidic screening system

Abstract

Graphical abstractDisplay Omitted Highlights? We use a microfluidic chamber to investigate the cell rolling. ? We examine changes of cell behavior according to the hydrodynamic parameters. ? We schematize the cell behavior from firm adhesion to free rolling regime with the shear stress. ? We model the cell rolling accounting the adhesion force represented by a linear spring. ? The good fitting between numerical and experimental describes the cell behavior. Here we present a model and an experimental investigation to study cell bound to the floor of a microfluidic system and the flow induced detachment. The experimental investigation has been performed by a microfluidic assay biofunctionalized with specific antibodies. The upregulation of the cell membrane density of specific antigens has been exploited to detect and concentrate cells using hydrodynamic forces. The numerical model explored the role that the hydrodynamic forces have on adhesion-detachment of cell to the biofunctionalized substrate. To account the adhesion force, the cell receptor-surface ligand interaction has been represented by a linear spring exerting adhesive force on the target cell. The experimental investigation with the W6/32, an antibody that binds specifically to MHC class I molecule and which has an important role in the recognition of the tumor cells from the immune system, has been simulated by the numerical model with a constant spring Ks=7.5i?10-8N/s. The velocity of cells and of the fluid and the experimental capture yield have been compared. The existence of three different regimes of cell behavior has been shown, moving from firm adhesion to free rolling. Up to 30µl/s the cells experience the adherent rolling, whilst at higher flow rate the cells start to move with the fluid in a regime of free rolling. The model provides physical insight, explaining apparently counterintuitive features of the prototype assay data.