Mechanics of cellular deformation and adhesion in shear flow

Leukocyte adhesion to venular endothelium has widely been viewed as a central event in the inflammatory response that precedes leukocytes emigration through the microvessel wall. The process of leukocyte adhesion and rolling along endothelium involves a complex balance of forces arising from hydrodynamic shearing effects and the strength of the adhesive bond between the leukocyte and endothelium. This balance depends strongly on leukocyte deformability and the expression of adhesion receptors and ligands. To elucidate the contribution of cell deformability to the strength of cell-surface adhesion, this study was designed toward developing an in vitro experimental method for the study of cell deformation and adhesion to various adhesive surfaces under dynamic flow conditions. In contrast to the conventional parallel-plate flow chamber which can only provide top views of cells in contact with the substrate, the designed side-view flow chamber permits the observations of side or top view of cells as well as detailed morphological changes of cells in contact with an adhesive surface in shear flow. Specifically, the relationship between cell deformability and cell detachment time during spontaneous intermittent adhesion was obtained. The study used the method of observing T-leukemic Jurkat cells interacting with ICAM-1 coated glass surfaces under various shear stresses. To further demonstrate whether an increase in cell deformability or ligand density would result in longer adhesion time, measurements of cell shape and cell detachment time were performed by treating Jurkat cells with chemical agents or by increasing the concentration of the ICAM-1 molecule coating.; In addition, a biomechanical model using the theory of an elastic thin shell coupled with adhesion bond reaction kinetics was presented to find the relationship between cell membrane mechanics and the formation and disruption of adhesion bonds. A finite element computational method was utilized to calculate the hydrodynamic force and torque exerted on cells. The equilibrium among forces arising from hydrodynamic shearing effects due to the blood flow, the strength of the adhesive bond between cell and substrate was considered. Results are presented which show the relative influence of cell deformability and adhesion kinetics on the cell attachment and detachment process.