Browsing by Author "Balagam, Rajesh"
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Item Mechanism for Collective Cell Alignment inᅠ Myxococcus xanthus Bacteria(Public Library of Science, 2015) Balagam, Rajesh; Igoshin, Oleg A.; Center for Theoretical Biological PhysicsMyxococcus xanthusᅠcells self-organize into aligned groups, clusters, at various stages of their lifecycle. Formation of these clusters is crucial for the complex dynamic multi-cellular behavior of these bacteria. However, the mechanism underlying the cell alignment and clustering is not fully understood. Motivated by studies of clustering in self-propelled rods, we hypothesized thatᅠM.ᅠxanthusᅠcells can align and form clusters through pure mechanical interactions among cells and between cells and substrate. We test this hypothesis using an agent-based simulation framework in which each agent is based on the biophysical model of an individualᅠM.ᅠxanthusᅠcell. We show that model agents, under realistic cell flexibility values, can align and form cell clusters but only when periodic reversals of cell directions are suppressed. However, by extending our model to introduce the observed ability of cells to deposit and follow slime trails, we show that effective trail-following leads to clusters in reversing cells. Furthermore, we conclude that mechanical cell alignment combined with slime-trail-following is sufficient to explain the distinct clustering behaviors observed for wild-type and non-reversingᅠM.ᅠxanthusᅠmutants in recent experiments. Our results are robust to variation in model parameters, match the experimentally observed trends and can be applied to understand surface motility patterns of other bacterial species.Item Myxococcus xanthus Gliding Motors Are Elastically Coupled to the Substrate as Predicted by the Focal Adhesion Model of Gliding Motility(Public Library of Science, 2014) Balagam, Rajesh; Litwin, Douglas B.; Czerwinski, Fabian; Sun, Mingzhai; Kaplan, Heidi B.; Shaevitz, Joshua W.; Igoshin, Oleg A.Myxococcus xanthus is a model organism for studying bacterial social behaviors due to its ability to form complex multi-cellular structures. Knowledge of M. xanthus surface gliding motility and the mechanisms that coordinated it are critically important to our understanding of collective cell behaviors. Although the mechanism of gliding motility is still under investigation, recent experiments suggest that there are two possible mechanisms underlying force production for cell motility: the focal adhesion mechanism and the helical rotor mechanism, which differ in the biophysics of the cell-substrate interactions. Whereas the focal adhesion model predicts an elastic coupling, the helical rotor model predicts a viscous coupling. Using a combination of computational modeling, imaging, and force microscopy, we find evidence for elastic coupling in support of the focal adhesion model. Using a biophysical model of the M. xanthus cell, we investigated how the mechanical interactions between cells are affected by interactions with the substrate. Comparison of modeling results with experimental data for cell-cell collision events pointed to a strong, elastic attachment between the cell and substrate. These results are robust to variations in the mechanical and geometrical parameters of the model. We then directly measured the motor-substrate coupling by monitoring the motion of optically trapped beads and find that motor velocity decreases exponentially with opposing load. At high loads, motor velocity approaches zero velocity asymptotically and motors remain bound to beads indicating a strong, elastic attachment.Item Role of mechanical interactions in self-organization behaviors of Myxococcus xanthus bacteria(2017-03-14) Balagam, Rajesh; Igoshin, Oleg ACoordinated cell movement and intercellular interactions are crucial for bacterial multicellularity and self-organization, and the mechanisms governing these processes are of active scientific interest. Individual cells interact with neighbors through various biochemical and mechanical interactions, but the role of mechanical interactions in coordination and selforganization of bacteria remains unclear. This work investigates the mechanisms underlying various multicellular patterns in Myxococcus xanthus bacteria, a model organism to study self-organization in bacteria, and the role of mechanical interactions in these self-organization behaviors using biophysical models of cell motility in an agent-based-simulation framework. Using this framework, first I studied the mechanism of gliding cell motility in M. xanthus by discriminating motility behavior of biophysical model cells during physical cell collisions from two alternative cell motility models proposed in the literature. Comparing the model cell motility behavior with experimental cell collision behavior showed that gliding cell motility in M. xanthus requires strong cell-substrate interactions supporting one of the proposed models. New predictions from this model are independently verified in direct experimentation. Next, I investigated the mechanisms responsible for formation and alignment of M. xanthus cells in groups and their collective movement in circular and spiral patterns under starvation, by simulating intercellular interactions among a large number of model cells. Results from the simulations show that these collective cell behaviors in M. xanthus can be explained through mechanical and biochemical interactions among cells and with the substrate. Finally, I investigated the mechanism for non-monotonic colony expansion behavior observed in M. xanthus motility mutants using the agent-based-simulation framework and analyzed individual cell motility behavior from experiments under similar conditions. Results from this work provide evidence that cell-stalling, a crucial assumption made by previous models to explain non-monotonic colony expansion, does not occur due to physical interactions and is not observed in experimental M. xanthus swarms. Results from this thesis work show that many self-organization behaviors in M. xanthus can be explained by a combination of mechanical interactions among cells, between the cells and the substrate and contact based biochemical signaling. This work improves our understanding of mechanisms governing various self-organization behaviors displayed by M. xanthus bacteria and provides a general framework to study self-organization behaviors in other surface motile bacteria.