Directional Persistence of Cell Migration Coincides with Stability of Asymmetric Intracellular Signaling

Abstract

It has long been appreciated that spatiotemporal dynamics of cell migration are under the control of intracellular signaling pathways, which are mediated by adhesion receptors and other transducers of extracellular cues. Further, there is ample evidence that aspects of cell migration are stochastic: how else could it exhibit directional persistence over timescales much longer than typical signal transduction processes, punctuated by abrupt changes in direction? Yet the mechanisms by which signaling processes affect those behaviors remain unclear. We have developed analytical methods for relating parallel live-cell microscopy measurements of cell migration dynamics to the intracellular signaling processes that govern them. In this analysis of phosphoinositide 3-kinase signaling in randomly migrating fibroblasts, we observe that hot spots of intense signaling coincide with localized cell protrusion and endure with characteristic lifetimes that correspond to those of cell migration persistence. We further show that distant hot spots are dynamically and stochastically coupled. These results are indicative of a mechanism by which changes in a cell's direction of migration are determined by a fragile balance of relatively rapid intracellular signaling processes.

Excitable Signal Transduction Networks in Directed Cell Migration

“…One study shows that spontaneous, dynamic PI3K activation occurs in neutrophils which have been immobilized by a cocktail of cytoskeletal inhibitors (Wang et al, 2014). The theme of independent coupled networks was advanced by studies demonstrating a spatio-temporal association of larger waves of cytoskeletal activities with STEN reporters (Weiger et al, 2010). Furthermore, in cells migrating over perforations, F-actin is polymerized at points of high curvature but only in regions of accumulation of PIP3 (Jasnin et al, 2016).…”

Linking morphodynamics and directional persistence of T lymphocyte migration

“…These results suggest that the fates of bifurcated lamellipodia are not entirely random, and that there might be distinct modes of T-cell migration associated with the tendency to turn. To compare these temporal characteristics of lamellipodial bifurcation to those of the overall cell movement, we calculated the autocorrelation coefficient of the cell movement vector with varying time lag [17]. The analysis shows a rapid loss of correlated movement, within approximately 0.5 min, but also persistent positive correlation over longer periods of observation (figure 3c).…”

Segmentation-based Image Analysis Tool for Surveying and Statistical Applications

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“…It is also important in geological survey and research, considering the requirement of analysis of geographical maps and images repeatedly [9][10][11][12][13]. Systematic image analysis also provides valuable data extracted from images to be utilized in statistical analysis [7,14,15]. There being many available tools for analyzing images; most of them lacks universal suitability, appropriateness and flexibility for varying applications.…”

“…Computational language-based image analysis approach offers the flexibilities without the limitations of the commercial software. Because of the simplicity, widespread applicability and customization options, image analysis using MATLABbased custom codes has already gained popularity in many perspectives [7,[16][17][18]. Wide range of images can be analyzed using algebraic theories and functions building up particular unique algorithm for each task.…”