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dc.titleA computational model of mutual antagonism in the mechano-signaling network of RhoA and nitric oxide
dc.contributor.authorSurendran, Akila
dc.contributor.authorForbes Dewey C., Jr
dc.contributor.authorLow, Boon Chuan
dc.contributor.authorTucker-Kellogg, Lisa
dc.identifier.citationSurendran, 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.
dc.description.abstractBackground: 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).
dc.publisherBioMed Central Ltd
dc.rightsAttribution 4.0 International
dc.sourceScopus OA2021
dc.subjectBistable network
dc.subjectDynamical systems
dc.subjectMutual antagonism
dc.subjectNitric oxide
dc.contributor.departmentSINGAPORE-MIT ALLIANCE
dc.contributor.departmentUNIVERSITY SCHOLARS PROGRAMME
dc.contributor.departmentDUKE-NUS MEDICAL SCHOOL
dc.description.sourcetitleBMC Molecular and Cell Biology
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