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

W. K. Ajith Karunarathne, Lopamudra Giri, Anilkumar K. Patel, Kareenhalli V. Venkatesh, N. Gautam

Research output: Contribution to journalArticle

39 Scopus citations

Abstract

There is a dearth of approaches to experimentally direct cell migration by continuously varying signal input to a single cell, evoking all possible migratory responses and quantitatively monitoring the cellular and molecular response dynamics. Here we used a visual blue opsin to recruit the endogenous G-protein network that mediates immune cell migration. Specific optical inputs to this optical trigger of signaling helped steer migration in all possible directions with precision. Spectrally selective imaging was used to monitor cell-wide phosphatidylinositol (3,4,5)-triphosphate (PIP3), cytoskeletal, and cellular dynamics. 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 incorporatinga 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.

Original languageEnglish
Pages (from-to)E1575-E1583
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number17
DOIs
StatePublished - Apr 23 2013

Keywords

  • Optogenetics
  • Ultrasensitivity

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