Venkatesh Lab

Chemotaxis in immune cells


A switch-like PIP3 increase at the cell front and a decrease at the back were identified, underlying the decisive migratory response. Migration was initiated at the rapidly increasing switch stage of PIP3 dynamics. This result explains how a migratory cell filters background fluctuations in the intensity of an extracellular signal but responds by initiating directionally sensitive migration to a persistent signal gradient across the cell. A two-compartment computational model incorporating a localized activator that is antagonistic to a diffusible inhibitor was able to simulate the switch-like PIP3 response. It was also able simulate the slow dissipation of PIP3 on signal termination. The ability to independently apply similar signaling inputs to single cells detected two cell populations with distinct thresholds for migration initiation. Overall the optical approach here can be applied to understand G-protein–coupled receptor network control of other cell behaviors.





Optical control demonstrates switch-like PIP3 dynamics underlying the initiation of immune cell migration,

WKA Karunarathne, L Giri, AK Patel, KV Venkatesh, N Gautam, Proceedings of the National Academy of Sciences 110 (17), E1575-E1583, 2013.