“The cell’s compass: A local-excitation, global-inhibition biased excitable network controls temporal and spatial responses to chemoattractants”
Dr. Pablo A. Iglesias, Johns Hopkins University
Cells have an internal compass that enables them to move along shallow chemical gradients. As amoeboid cells migrate, signaling events are spontaneously activated on pseudopodia. The addition of spatially uniform chemoattractant stimulus triggers a symmetric response, whereupon cells stop and round up. Localized patches of activity then appear as cells spread. Finally cells adapt and resume random migration. In contrast, in the presence of chemotactic gradients cells continuously direct signaling events to the front of the cell. Local-excitation, global-inhibition (LEGI) and reaction-diffusion models have captured some of these features of chemotaxing cells, but no system has explained the complex response kinetics, the sensitivity to shallow gradients or the role of recently observed propagating waves within the actin cytoskeleton.
In this talk I discuss the LEGI-biased excitable network hypothesis. We use it to formulate a mathematical model that simulates most of the behaviors of chemotactic cells. In the absence of stimulation, spontaneous spots of activity appear around the cell cortex. Chemoattractant stimulus increments trigger an initial burst of patches of activity, followed by localized secondary events. After a few minutes, the system adapts, again displaying random activity. In gradients, the activity patches are directed continuously and selectively toward the chemoattractant, providing an extraordinary degree of amplification. Importantly, by perturbing model parameters, we generate distinct behaviors consistent with known classes of mutants.
This work brings heretofore diverse observations on spontaneous cytoskeletal activity, signaling responses to temporal stimuli and spatial gradient sensing into a unified scheme. This is joint work with Yuan Xiong, Peter Devreotes and Chuan-Hsiang Huang.