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A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide

Author(s)
Surendran, Akila; Forbes Dewey, C.; Low, Boon C.; Tucker-Kellogg, Lisa
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Creative Commons Attribution https://creativecommons.org/licenses/by/4.0/
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Abstract
Abstract Background RhoA is a master regulator of cytoskeletal contractility, while nitric oxide (NO) is a master regulator of relaxation, e.g., vasodilation. There are multiple forms of cross-talk between the RhoA/ROCK pathway and the eNOS/NO/cGMP pathway, but previous work has not studied their interplay at a systems level. Literature review suggests that the majority of their cross-talk interactions are antagonistic, which motivates us to ask whether the RhoA and NO pathways exhibit mutual antagonism in vitro, and if so, to seek the theoretical implications of their mutual antagonism. Results Experiments found mutual antagonism between RhoA and NO in epithelial cells. Since mutual antagonism is a common motif for bistability, we sought to explore through theoretical simulations whether the RhoA-NO network is capable of bistability. Qualitative modeling showed that there are parameters that can cause bistable switching in the RhoA-NO network, and that the robustness of the bistability would be increased by positive feedback between RhoA and mechanical tension. Conclusions We conclude that the RhoA-NO bistability is robust enough in silico to warrant the investment of further experimental testing. Tension-dependent bistability has the potential to create sharp concentration gradients, which could contribute to the localization and self-organization of signaling domains during cytoskeletal remodeling and cell migration.
Date issued
2021-10-12
URI
https://hdl.handle.net/1721.1/136743
Department
Singapore-MIT Alliance in Research and Technology (SMART); Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Mechanical Engineering
Publisher
BioMed Central
Citation
BMC Molecular and Cell Biology. 2021 Oct 12;22(Suppl 1):47
Version: Final published version

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