HAMMER, D.A.*; KING, M.R.; TEES, D.F.J.; RODGERS, S.D.; EVANS, E.A.; CAMPHAUSEN, R.T.: Dynamics and Biomechanics in Leukocyte Adhesion: from molecular properties to the behavior of many cells

Leukocytes perform immunological functions in the body. Part of their function is home to sites of disease. Interestingly, receptor-mediated leukocyte adhesion in blood vessels involves two steps: rolling, mediated by binding between selectins and carbohydrate bearing ligands, and firm adhesion, mediated by integrins. We are trying to understand the molecular properties of different adhesion molecules, and why different molecules mediate different dynamic states of adhesion. We have recreated rolling adhesion by putting well defined selectin ligands on polystyrene microspheres. These experiments have identified how small differences in chemistry can have large effects on the dynamics of rolling. Also, we have simulated the dynamics of adhesion using computation, mapping the properties of individual adhesion molecules to the dynamics of adhesion itself. We have measured the properties of individual adhesion molecules using dynamic force spectroscopy. Recently, we have been able to reconcile measurements of single bond properties with the dynamics of adhesion through computer simulations. Finally, we have sought to understand cooperative phenomena that occurs among cells through the combined action of cell-cell hydrodynamic and molecular interactions. We have elucidated several mechanisms by which cells influence each other’s motion. These phenomena have been measured in flow chambers and simulated using a new algorithm that combines molecular and cellular interactions. These investigations provide us with a continuum of investigation of biological adhesion from molecules to the level of many cells.