Modeling the self-organized phosphatidylinositol lipids signaling system in chemotactic cells based on quantitative image analysis

Advance Online Publication August 16, 2012 doi: 10.1242/?jcs.108373 The phosphatidylinositol (PtdIns) lipids reaction is a key signaling event; this signal is responsible for gradient sensing in eukaryotic cell chemotaxis. The self-organization activity of the PtdIns lipids reaction induces an inherent polarity even in the absence of an external chemoattractant gradient by producing a localized PtdIns 3,4,5-trisphosphate [PtdIns(3,4,5)P3]-enriched domain on the membrane. Experimentally, we found that such a domain could exhibit two types of behavior: 1) persistent domain formation that travels on the membrane and 2) stochastic formation of transient domains. Taking advantage of the simultaneous visualization of PtdIns(3,4,5)P3 and its enzyme, phosphatase and a tensin homolog (PTEN), the inter-dependence of their spatiotemporal dynamics was demonstrated statistically. Based on this statistical analysis, we developed a theoretical model for the self-organization of PtdIns lipids signaling that can accurately reproduce both persistent and transient domain formation; these types of formations can be explained by the oscillatory and excitability properties of the system, respectively.

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