Published in: Integrative Biology (2019)
In this paper, we took a previously published model of T cell trafficking and extended it to include the functions of kindlin-3, a protein which mediates the conversion of LFA-1 from an intermediate affinity form to the high affinity form used to arrest on the endothelium. Our simulations predicted that lymphocyte adhesion would be hypersensitive to the level of kindlin-3, which we then predicted through genetic perturbation of a model cell line along with comparisons to literature. Especially exciting for us was that the predictions were quantitatively accurate. This suggests that Adhesive Dynamics simulations can used to predict the effect of changing protein levels or kinetic constants on the ability of cells to adhere to endothelium.
Nicholas R. Anderson 