572aq

Modeling the Mechanical Behavior of Leukocytes as Elastic Solids In Micropipette Aspiration Indentation Experiments

David J. Gee1, Elena Lomakina2, Richard E. Waugh1, and Michael R. King3. (1) Biomedical Engineering, University of Rochester, Goergen Hall, Rochester, NY 14627, (2) Pharmacology & Physiology, University of Rochester, Goergen Hall, Rochester, NY 14627, (3) Biomedical & Chemical Engineering, University of Rochester, Goergen Hall, Rochester, NY 14627

The initial events of the inflammatory cascade in the microcirculation include the formation of transient tether bonds between leukocytes and endothelium. The coordinated association and subsequent dissociation of these molecular bonds is primarily effected by selectins and their corresponding counter-receptors and induces cell rolling motion along the endothelium whereby the leukocyte effectively integrates chemical and molecular signals of inflammation. During this phase of inflammatory response, cell deformation is relatively small and the rolling cell generally maintains its spherical shape. We have developed a computer simulation of the cell as an elastic solid in order to model small-scale cell deformation during this phase. Recently, we published data from cell-bead indentation experiments whereby a rigid bead indents and subsequently induces deformation of a neutrophil during controlled impingement. Additionally, we formulated an analytical description of the interfacial contact area as a function of impingement force and cell-bead geometry. In the current study, the Deformable Multiparticle Adhesive Dynamics (DMAD) simulation was used to compute the interfacial contact area during such impingement and was found to show similar agreement in the force-area relationship in the deformation regime where a linear elastic model is applicable. The resulting model will have great utility in modeling multicellular recruitment during inflammation and the effect of cell deformation in enhancing cell adhesion under flow.

Keywords: leukocyte deformation, micropipette aspiration, computer simulation