Mathematical Biology Seminar

Wendy Thomas
University of Washington

Mathematical modeling relates cell adhesion to molecular properties

Wednesday, March 6, 2013, at 3:05pm
LCB 219

Many blood cells and pathogens bind to other cells or tissues in the presence of flowing fluid. These diverse cells have evolved mechanisms to withstand and even utilize the associated drag forces to strengthen adhesion, so that many of them display a shear enhanced adhesion in which they detach at low shear but roll along the tissue surface or even stick firmly at higher shear. In this talk we use Escherichia coli as a model system to determine the role of various molecules in this counterintuitive behavior. We use force spectroscopy to characterize the mechanical properties of simple molecular complexes, including the adhesive molecules of E. coli, which form catch bonds that are longer lived under increased tensile force, and the tethers anchoring these bonds, which elongate long distances at a constant force. We develop mathematical models that describe these molecular behaviors quantitatively, and then incorporate these models into simulations of whole cell adhesion, to explain how each property contributes to the observed behaviors. Other pathogens and blood cells display convergent evolution, because their adhesive bonds and tethers catch and elongate with similar mechanical properties as those of E. coli, although they have no genetic or structural similarities. This suggests that the principles established from studying this model system can be extended to a large number of cells adhering in flow.