IAM – PIMS Distinguished Colloquium: Dan Hammer

Adhesive Dynamics is a method to simulate the dynamics of cell adhesion to surfaces. Adhesion receptors are modeled as reactive mechanical entities with adhesive tips, and the formation and breakage of adhesion molecules with cognate ligands is simulated using random number sampling. Once the bonds form, the contact points they make with surfaces are tracked, and a force balance is used to calculate the motion of the cell. Specific rheological laws relate stress (or strain) to bond failure rates, and the parameters of these laws dictate the quantitative sensitivity of adhesion molecules to force, and ultimately affect the dynamics of cell adhesion as a whole. We summarize major findings of cell adhesion that have been enabled by Adhesive Dynamics - the development of state diagrams of adhesion, that link distinct states of adhesion to molecular identity, such as leukocyte rolling; specification of what is required for firm arrest of a leukocyte; a description of the shear threshold effect in which adhesion increases with shear rate; and understanding how two molecules can act in synergy to secure adhesion that cannot be secured by either molecule alone. Finally, we show how signal transduction networks can be integrated within adhesive dynamics to understand how cell activation can lead to changes in adhesion and arrest, and use predictions to understand how cells might behave when molecular components are altered or eliminated in knock-out mice, or in various diseases due to molecular defects.