A rate equation approach to elucidate the kinetics and robustness of the TGF-beta pathway
(2006) In Biophysical Journal 91(12). p.4368-4380- Abstract
- We present a rate equation model for the TGF-beta pathway in endothelial cells together with novel measurements. This pathway plays a prominent role in inter- and intracellular communication and subversion can lead to cancer, fibrosis vascular disorders, and immune diseases. The model successfully describes the kinetics of experimental data and also correctly predicts the behavior in experiments where the system is perturbed. A novel method in this context, simulated tempering, is used to fit the model parameters to the data. It provides an ensemble of high quality solutions, which are analyzed with clustering methods and display a hierarchical structure highlighting distinct parameter subspaces with biological interpretations. This... (More)
- We present a rate equation model for the TGF-beta pathway in endothelial cells together with novel measurements. This pathway plays a prominent role in inter- and intracellular communication and subversion can lead to cancer, fibrosis vascular disorders, and immune diseases. The model successfully describes the kinetics of experimental data and also correctly predicts the behavior in experiments where the system is perturbed. A novel method in this context, simulated tempering, is used to fit the model parameters to the data. It provides an ensemble of high quality solutions, which are analyzed with clustering methods and display a hierarchical structure highlighting distinct parameter subspaces with biological interpretations. This analysis discriminates between different biological mechanisms to achieve a transient signal from a sustained TGF-beta input, where one mechanism is to use a negative feedback to turn the signal off. Further analysis in terms of parameter sensitivity reveals that this negative feedback loop in TGF-beta signaling renders the system global robustness. This sheds light upon the role of the Smad7 protein in this system. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/685725
- author
- Melke, Pontus LU ; Jönsson, Henrik LU ; Pardali, Evangelia LU ; ten Dijke, Peter and Peterson, Carsten LU
- organization
- publishing date
- 2006
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Biophysical Journal
- volume
- 91
- issue
- 12
- pages
- 4368 - 4380
- publisher
- Cell Press
- external identifiers
-
- wos:000242339600006
- scopus:33845424529
- ISSN
- 1542-0086
- DOI
- 10.1529/biophysj.105.080408
- language
- English
- LU publication?
- yes
- id
- 59e927a9-4f02-4464-8eda-ae57b8fe3a45 (old id 685725)
- alternative location
- http://dx.doi.org/10.1529/biophysj.105.080408
- date added to LUP
- 2016-04-01 11:48:47
- date last changed
- 2023-01-02 23:45:16
@article{59e927a9-4f02-4464-8eda-ae57b8fe3a45,
abstract = {{We present a rate equation model for the TGF-beta pathway in endothelial cells together with novel measurements. This pathway plays a prominent role in inter- and intracellular communication and subversion can lead to cancer, fibrosis vascular disorders, and immune diseases. The model successfully describes the kinetics of experimental data and also correctly predicts the behavior in experiments where the system is perturbed. A novel method in this context, simulated tempering, is used to fit the model parameters to the data. It provides an ensemble of high quality solutions, which are analyzed with clustering methods and display a hierarchical structure highlighting distinct parameter subspaces with biological interpretations. This analysis discriminates between different biological mechanisms to achieve a transient signal from a sustained TGF-beta input, where one mechanism is to use a negative feedback to turn the signal off. Further analysis in terms of parameter sensitivity reveals that this negative feedback loop in TGF-beta signaling renders the system global robustness. This sheds light upon the role of the Smad7 protein in this system.}},
author = {{Melke, Pontus and Jönsson, Henrik and Pardali, Evangelia and ten Dijke, Peter and Peterson, Carsten}},
issn = {{1542-0086}},
language = {{eng}},
number = {{12}},
pages = {{4368--4380}},
publisher = {{Cell Press}},
series = {{Biophysical Journal}},
title = {{A rate equation approach to elucidate the kinetics and robustness of the TGF-beta pathway}},
url = {{https://lup.lub.lu.se/search/files/2652984/1266238.pdf}},
doi = {{10.1529/biophysj.105.080408}},
volume = {{91}},
year = {{2006}},
}