Title: Gradient sensing by eucaryotic cells: Signaling mechanisms and spatiotemporal dynamics
Speaker: Atul Narang, University of Florida
Date: Wednesday, April 21, 2004, 1:00 pm
Location: Hill Center, Room 260, Rutgers University, Busch Campus, Piscataway, NJ
The crawling movement of cells in response to an external chemical gradient is a complex process which requires the coordination of many intracellular reactions. A complete description of the mechanisms associated with cell movement remains elusive, but the very first step of gradient sensing, enabling the cell to "see" the external gradient, is becoming more transparent. The increased understanding of gradient sensing has been driven by the discovery that within 5-10 seconds of applying a shallow chemical gradient, certain membrane phospholipids localize at the front end of the cell. This phospholipid localization lies at the heart of gradient sensing.
The simplest explanation for the the strong localization of the phospholipids is that the gradient sensing mechanism merely amplifies the external signal. However, experiments preclude this simple model because the cells polarize even in the absence of a gradient. Similarly, even if the cells are exposed to multiple sources, the phospholipids localize at only one location. These dynamics suggest that the gradient sensing response involves more than simple amplification of the external signal.
I will begin by presenting experimental data on the phosphoinositide dynamics observed in response to various chemoattractant perturbations. I will then show that a simple nonlinear reaction-diffusion model based on the molecular mechanisms of the phosphoinositide cycle captures both the steady state patterns and the dynamics of the phosphoinositide distributions. The model is formally similar to models from combustion theory that exhibit temperature "hotspots".
Seminar sponsored by DIMACS/BIOMAPS Seminar Series on Quantitative Biology and Epidemiology.