Abstract
Many eukaryotic cells are able to crawl on surfaces and guide their motility based on environmental cues. These cues are interpreted by signaling systems which couple to cell mechanics; indeed membrane protrusions in crawling cells are often accompanied by activated membrane patches, which are localized areas of increased concentration of one or more signaling components. To determine how these patches are related to cell motion, we examine the spatial localization of RasGTP in chemotaxing Dictyostelium discoideum cells under conditions where the vertical extent of the cell was restricted. Quantitative analyses of the data reveal a high degree of spatial correlation between patches of activated Ras and membrane protrusions. Based on these findings, we formulate a model for amoeboid cell motion that consists of two coupled modules. The first module utilizes a recently developed two-component reaction diffusion model that generates transient and localized areas of elevated concentration of one of the components along the membrane. The activated patches determine the location of membrane protrusions (and overall cell motion) that are computed in the second module, which also takes into account the cortical tension and the availability of protrusion resources. We show that our model is able to produce realistic amoeboid-like motion and that our numerical results are consistent with experimentally observed pseudopod dynamics. Specifically, we show that the commonly observed splitting of pseudopods can result directly from the dynamics of the signaling patches.
Highlights
Directional cellular migration is a widely observed phenomenon, ranging from mammalian cells to unicellular eukaryotes to bacteria
We used Ras binding domain (RBD)-GFP to track the localization of RasGTP at the cell membrane in chemotaxing Dictyostelium cells at 2 second intervals
Several recent studies have demonstrated that Ras activation is upstream of F-actin polymerization in a causal sequence leading to the formation of membrane protrusions and pseudopods [7,22,26,27]
Summary
Directional cellular migration is a widely observed phenomenon, ranging from mammalian cells to unicellular eukaryotes to bacteria. As well as in mature organisms, cells respond to environmental cues and migrate to distant sites to perform different tasks, such as wound healing or immune response [1]. Directional motion according to external cues, known as chemotaxis, is typically controlled by signaling processes in the cell. The external stimulation leads to internal symmetry breaking and to the formation of a distinct front and back. This sensing step is coupled to cell mechanics, which is governed by signaling processes which are highly conserved between different organisms [6]
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