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Experimentally guided computational model discovers important elements for social behavior in myxobacteria.

Hendrata M, Yang Z, Lux R, Shi W - PLoS ONE (2011)

Bottom Line: The simulation is able to produce both gliding pattern and spontaneous aggregation center formation as observed in experiments.The model is tested against several known M. xanthus mutants and our modification of parameter values relevant for the individual mutants produces good phenotypic agreements.This outcome indicates the strong predictive potential of our model for the social behaviors of uncharacterized mutants and their expected phenotypes during development.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, California State University Los Angeles, Los Angeles, California, United States of America. mhendra@calstatela.edu

ABSTRACT
Identifying essential factors in cellular interactions and organized movement of cells is important in predicting behavioral phenotypes exhibited by many bacterial cells. We chose to study Myxococcus xanthus, a soil bacterium whose individual cell behavior changes while in groups, leading to spontaneous formation of aggregation center during the early stage of fruiting body development. In this paper, we develop a cell-based computational model that solely relies on experimentally determined parameters to investigate minimal elements required to produce the observed social behaviors in M. xanthus. The model verifies previously known essential parameters and identifies one novel parameter, the active turning, which we define as the ability and tendency of a cell to turn to a certain angle without the presence of any obvious external factors. The simulation is able to produce both gliding pattern and spontaneous aggregation center formation as observed in experiments. The model is tested against several known M. xanthus mutants and our modification of parameter values relevant for the individual mutants produces good phenotypic agreements. This outcome indicates the strong predictive potential of our model for the social behaviors of uncharacterized mutants and their expected phenotypes during development.

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Aggregation center formation of wild-type cells at the end of 12 hours under developmental conditions.(A) Simulation image using all five parameters with values listed in Table 1. Simulation uses periodic boundary conditions and starts with 5000 cells for 12 hours (2160 simulation time steps). (B) Experimental image showing early aggregation centers at 12 hours after initiation of starvation. Cells are shown in dark grey and EPS in white. Arrows show aggregation centers formed by large number of cells with high concentration of EPS. At locations with high EPS concentration, bright white color overrides black in the view of microscope.
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pone-0022169-g003: Aggregation center formation of wild-type cells at the end of 12 hours under developmental conditions.(A) Simulation image using all five parameters with values listed in Table 1. Simulation uses periodic boundary conditions and starts with 5000 cells for 12 hours (2160 simulation time steps). (B) Experimental image showing early aggregation centers at 12 hours after initiation of starvation. Cells are shown in dark grey and EPS in white. Arrows show aggregation centers formed by large number of cells with high concentration of EPS. At locations with high EPS concentration, bright white color overrides black in the view of microscope.

Mentions: In the next simulation (Fig. 3A), we start from a higher cell density and test whether the five cellular properties are sufficient to produce initial aggregation centers similar to those observed in M. xanthus development assay (Fig. 3B). We simulate 5000 M. xanthus cells, with all five parameters that are set according to values listed in Table 1. The cells are initially placed randomly over the simulation domain with periodic boundary conditions, where they start to glide independently of each other. During gliding, they deposit EPS slime and follow existing slime trails. At this early stage, cells reverse their polarity periodically and their frequent turns are due to either collision between cells, EPS slime following, or the active turning itself. As several cells follow the same trail, they form small groups and move together in streams. Individual cells often join the streams, which results in increasing local cell density inside the streams. Due to the quorum sensing mechanism, cells that locate at a higher neighboring density modulate their reversal frequency. Streaming cells do not reverse as frequently as before and thus travel farther. As local cell density keeps increasing, cells in streams begin to turn to one direction once they encounter an area with high EPS slime concentration. This one directional turning event results in the formation of a circular path. With many cells following this path, it gradually forms an initial aggregation center in which cells orbit in spiral patterns. More cells are absorbed to this center causing it to become more condensed. At this stage, few cells leave the center occasionally and some may reverse to rejoin the center. Since we only simulate a fixed, limited number of cells approximately 90% of cells join the aggregation center at the end of 12 hours, leaving few cells gliding independently outside. This new model exactly reproduces different stages and the multicellular behavior during the aggregation center formation of M. xanthus development. Therefore, we demonstrate that the five parameters are not only necessary for creating the gliding pattern at low cell density but are essential in early aggregation center formation during M. xanthus development at higher cell density.


Experimentally guided computational model discovers important elements for social behavior in myxobacteria.

Hendrata M, Yang Z, Lux R, Shi W - PLoS ONE (2011)

Aggregation center formation of wild-type cells at the end of 12 hours under developmental conditions.(A) Simulation image using all five parameters with values listed in Table 1. Simulation uses periodic boundary conditions and starts with 5000 cells for 12 hours (2160 simulation time steps). (B) Experimental image showing early aggregation centers at 12 hours after initiation of starvation. Cells are shown in dark grey and EPS in white. Arrows show aggregation centers formed by large number of cells with high concentration of EPS. At locations with high EPS concentration, bright white color overrides black in the view of microscope.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3139613&req=5

pone-0022169-g003: Aggregation center formation of wild-type cells at the end of 12 hours under developmental conditions.(A) Simulation image using all five parameters with values listed in Table 1. Simulation uses periodic boundary conditions and starts with 5000 cells for 12 hours (2160 simulation time steps). (B) Experimental image showing early aggregation centers at 12 hours after initiation of starvation. Cells are shown in dark grey and EPS in white. Arrows show aggregation centers formed by large number of cells with high concentration of EPS. At locations with high EPS concentration, bright white color overrides black in the view of microscope.
Mentions: In the next simulation (Fig. 3A), we start from a higher cell density and test whether the five cellular properties are sufficient to produce initial aggregation centers similar to those observed in M. xanthus development assay (Fig. 3B). We simulate 5000 M. xanthus cells, with all five parameters that are set according to values listed in Table 1. The cells are initially placed randomly over the simulation domain with periodic boundary conditions, where they start to glide independently of each other. During gliding, they deposit EPS slime and follow existing slime trails. At this early stage, cells reverse their polarity periodically and their frequent turns are due to either collision between cells, EPS slime following, or the active turning itself. As several cells follow the same trail, they form small groups and move together in streams. Individual cells often join the streams, which results in increasing local cell density inside the streams. Due to the quorum sensing mechanism, cells that locate at a higher neighboring density modulate their reversal frequency. Streaming cells do not reverse as frequently as before and thus travel farther. As local cell density keeps increasing, cells in streams begin to turn to one direction once they encounter an area with high EPS slime concentration. This one directional turning event results in the formation of a circular path. With many cells following this path, it gradually forms an initial aggregation center in which cells orbit in spiral patterns. More cells are absorbed to this center causing it to become more condensed. At this stage, few cells leave the center occasionally and some may reverse to rejoin the center. Since we only simulate a fixed, limited number of cells approximately 90% of cells join the aggregation center at the end of 12 hours, leaving few cells gliding independently outside. This new model exactly reproduces different stages and the multicellular behavior during the aggregation center formation of M. xanthus development. Therefore, we demonstrate that the five parameters are not only necessary for creating the gliding pattern at low cell density but are essential in early aggregation center formation during M. xanthus development at higher cell density.

Bottom Line: The simulation is able to produce both gliding pattern and spontaneous aggregation center formation as observed in experiments.The model is tested against several known M. xanthus mutants and our modification of parameter values relevant for the individual mutants produces good phenotypic agreements.This outcome indicates the strong predictive potential of our model for the social behaviors of uncharacterized mutants and their expected phenotypes during development.

View Article: PubMed Central - PubMed

Affiliation: Department of Mathematics, California State University Los Angeles, Los Angeles, California, United States of America. mhendra@calstatela.edu

ABSTRACT
Identifying essential factors in cellular interactions and organized movement of cells is important in predicting behavioral phenotypes exhibited by many bacterial cells. We chose to study Myxococcus xanthus, a soil bacterium whose individual cell behavior changes while in groups, leading to spontaneous formation of aggregation center during the early stage of fruiting body development. In this paper, we develop a cell-based computational model that solely relies on experimentally determined parameters to investigate minimal elements required to produce the observed social behaviors in M. xanthus. The model verifies previously known essential parameters and identifies one novel parameter, the active turning, which we define as the ability and tendency of a cell to turn to a certain angle without the presence of any obvious external factors. The simulation is able to produce both gliding pattern and spontaneous aggregation center formation as observed in experiments. The model is tested against several known M. xanthus mutants and our modification of parameter values relevant for the individual mutants produces good phenotypic agreements. This outcome indicates the strong predictive potential of our model for the social behaviors of uncharacterized mutants and their expected phenotypes during development.

Show MeSH
Related in: MedlinePlus