A computational environment for the study of circulating cell mechanics and adhesion.

Specific cell adhesion is important in cell-mediated immunity, embryogenesis and wound healing. Understanding the adhesion process and the ability to manipulate it could lead to the therapeutic treatment of many disorders. Previous research has demonstrated that cell adhesion is governed by the coupling of several physical and biochemical forces which act on drastically different length scales. On the scale of the cell diameter are cell deformation and the flow of fluid external to the cell. At the gap near the area of contact (three orders of magnitude smaller) are specific molecular bonds and colloidal interactions. The complex coupling of these events and the different length scales at which they occur have complicated the studies of cell adhesion. Further difficulties arise from the fact that the mechanical behavior of most cells is not clearly defined. Cellular deformation has been studied for decades due to its relevance to whole blood dynamics, capillary occlusion and leukocyte extravasation. However, the constitutive relationship between stress and deformation for most cells is still elusive. The common procedure for testing hypotheses for such a relationship requires that the relationship be established a priori and that a new analytical set-up be developed for each relationship. In this thesis, a computational framework has been developed for the study of cell deformation and adhesion. As a tool to study cell mechanics, the program allows the incorporation of different mechanical models of the cell without significant changes in the set-up. As a tool to study cell adhesion, the program provides the coupling of the relevant forces and resolution of the different length-scales involved. Results using the code were found to agree well with experimental, analytical and other numerical solutions of various test cases. Simulations of cell-entry micropipet experiments showed that alternate models for the cell mechanics affect both the shape and the rate of entry of the cell entering the pipet. Finally, simulations of cells adhering under flow demonstrated that, for the parameters tried, the cell mechanics affect the size, shape and temporal evolution of the contact area, as well as the number of bonds existing at a given time.Ph.D.Applied SciencesBiological SciencesBiomedical engineeringCellular biologyMechanicsUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/129932/2/9711915.pd