Math Biology Seminar: Raibatak Das

Immune cells are activated when receptors on their surface bind to target pathogenic molecules. This leads to receptor phosphorylation, initiating a cascade of downstream signals. Advances in fluorescence microscopy have made it possible to watch this process unfold in real time on single cells. These experiments reveal a dynamic spatial reorganization of signaling molecules on the cell membrane: kinases (that phosphorylate receptor tyrosines) preferentially colocalize with the receptors, while phophatases are excluded away from them. This spatial reorganization is believed to promote receptor phosphorylation. In my talk, I will describe how we used single molecule tracks to quantify such spatial exclusion. We tracked molecules of CD45, a major tyrosine phosphatase in macrophages, around micropatterned, geometrical arrays of aggregated Fc receptors. We used molecular trajectories to compute detailed spatial statistics of CD45 and compared them with biophysical simulations. We inferred that aggregated receptors are surrounded by a molecular barrier that effectively restricted the diffusion of nearly 80% of CD45 molecules that would have otherwise entered these regions. I will present the details of this analysis and discuss the role of spatial segregation on signaling.