The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks
Many key biochemical reactions that mediate signal transduction in cells occur at the cell membrane, yet how the two-dimensional membrane environment influences the collective behavior of signaling networks is poorly understood. We study models of two topologically different signaling pathways that...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | en_US |
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American Chemical Society (ACS)
2014
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| Online Access: | http://hdl.handle.net/1721.1/91216 https://orcid.org/0000-0003-1268-9602 |
| _version_ | 1826193745770446848 |
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| author | Abel, Steven M. Roose, Jeroen P. Groves, Jay T. Weiss, Arthur Chakraborty, Arup K |
| author2 | Massachusetts Institute of Technology. Institute for Medical Engineering & Science |
| author_facet | Massachusetts Institute of Technology. Institute for Medical Engineering & Science Abel, Steven M. Roose, Jeroen P. Groves, Jay T. Weiss, Arthur Chakraborty, Arup K |
| author_sort | Abel, Steven M. |
| collection | MIT |
| description | Many key biochemical reactions that mediate signal transduction in cells occur at the cell membrane, yet how the two-dimensional membrane environment influences the collective behavior of signaling networks is poorly understood. We study models of two topologically different signaling pathways that exhibit bistability, examining the effects of reduced protein mobility and increased concentration at the membrane, as well as effects due to differences in spatiotemporal correlations between the membrane environment and three-dimensional cytoplasm. The two model networks represent the distributive enzymatic modification of a protein at multiple sites and the positive feedback-mediated activation of a protein. In both cases, we find that confining proteins to a membrane-like environment can markedly alter the emergent dynamics. For the distributive protein modification network, increased concentration promotes bistability through enhanced protein–protein binding, while lower mobility and membrane-enhanced spatiotemporal correlations suppress bistability. For the positive feedback-mediated activation network, confinement to a membrane environment enhances protein activation, which can induce bistability or stabilize a monostable, active state. Importantly, the influence of the membrane environment on signaling dynamics can be qualitatively different for signaling modules with different network topologies. |
| first_indexed | 2024-09-23T09:44:15Z |
| format | Article |
| id | mit-1721.1/91216 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:44:15Z |
| publishDate | 2014 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/912162022-09-30T16:31:22Z The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks Abel, Steven M. Roose, Jeroen P. Groves, Jay T. Weiss, Arthur Chakraborty, Arup K Massachusetts Institute of Technology. Institute for Medical Engineering & Science Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Chemical Engineering Massachusetts Institute of Technology. Department of Chemistry Ragon Institute of MGH, MIT and Harvard Abel, Steven M. Chakraborty, Arup K. Many key biochemical reactions that mediate signal transduction in cells occur at the cell membrane, yet how the two-dimensional membrane environment influences the collective behavior of signaling networks is poorly understood. We study models of two topologically different signaling pathways that exhibit bistability, examining the effects of reduced protein mobility and increased concentration at the membrane, as well as effects due to differences in spatiotemporal correlations between the membrane environment and three-dimensional cytoplasm. The two model networks represent the distributive enzymatic modification of a protein at multiple sites and the positive feedback-mediated activation of a protein. In both cases, we find that confining proteins to a membrane-like environment can markedly alter the emergent dynamics. For the distributive protein modification network, increased concentration promotes bistability through enhanced protein–protein binding, while lower mobility and membrane-enhanced spatiotemporal correlations suppress bistability. For the positive feedback-mediated activation network, confinement to a membrane environment enhances protein activation, which can induce bistability or stabilize a monostable, active state. Importantly, the influence of the membrane environment on signaling dynamics can be qualitatively different for signaling modules with different network topologies. National Institutes of Health (U.S.) (Director's Pioneer Award) National Institutes of Health (U.S.) (Grant 1P01AI091580-01) 2014-10-29T13:47:27Z 2014-10-29T13:47:27Z 2012-02 2012-02 Article http://purl.org/eprint/type/JournalArticle 1520-6106 1520-5207 http://hdl.handle.net/1721.1/91216 Abel, Steven M., Jeroen P. Roose, Jay T. Groves, Arthur Weiss, and Arup K. Chakraborty. “The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks.” The Journal of Physical Chemistry B 116, no. 11 (March 22, 2012): 3630–3640 https://orcid.org/0000-0003-1268-9602 en_US http://dx.doi.org/10.1021/jp2102385 Journal of Physical Chemistry B Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) PMC |
| spellingShingle | Abel, Steven M. Roose, Jeroen P. Groves, Jay T. Weiss, Arthur Chakraborty, Arup K The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks |
| title | The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks |
| title_full | The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks |
| title_fullStr | The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks |
| title_full_unstemmed | The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks |
| title_short | The Membrane Environment Can Promote or Suppress Bistability in Cell Signaling Networks |
| title_sort | membrane environment can promote or suppress bistability in cell signaling networks |
| url | http://hdl.handle.net/1721.1/91216 https://orcid.org/0000-0003-1268-9602 |
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