Month: September 2019

Published in: Biophysical Journal (2019)

This paper, written by my collaborator Alex Buffone, extends the paradigm of upstream migration in immune cells to neutrophils. Previous studies had suggested that these cells did not migrate upstream on ICAM-1 like other immune cells. Through the use of blocking antibodies and engineered surfaces, we proved that these cells will migrate upstream if Mac-1 is blocked. We believe that Mac-1 acts as a sink for ICAM-1, which prevents the engagement of LFA-1 and the resulting upstream migration.

DOI: 10.1016/j.bpj.2019.08.044

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.

Find this article on PubMed!

DOI: 10.1093/intbio/zyz024