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Title: A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide
Authors: Surendran, Akila 
Forbes Dewey C., Jr
Low, Boon Chuan 
Tucker-Kellogg, Lisa 
Keywords: Bistable network
Dynamical systems
Mutual antagonism
Nitric oxide
Issue Date: 1-Oct-2021
Publisher: BioMed Central Ltd
Citation: Surendran, Akila, Forbes Dewey C., Jr, Low, Boon Chuan, Tucker-Kellogg, Lisa (2021-10-01). A computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide. BMC Molecular and Cell Biology 22 : 47. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
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. © 2021, The Author(s).
Source Title: BMC Molecular and Cell Biology
ISSN: 2661-8850
DOI: 10.1186/s12860-021-00383-5
Rights: Attribution 4.0 International
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