The Interplay between Feedback and Buffering in Cellular Homeostasis
Buffering, the use of reservoirs of molecules to maintain concentrations of key molecular species, and negative feedback are the primary known mechanisms for robust homeostatic regulation. To our knowledge, however, the fundamental principles behind their combined effect have not been elucidated. He...
| Main Authors: | , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2017
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| _version_ | 1797092663771529216 |
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| author | Hancock, E Ang, J Papachristodoulou, A Stan, G |
| author_facet | Hancock, E Ang, J Papachristodoulou, A Stan, G |
| author_sort | Hancock, E |
| collection | OXFORD |
| description | Buffering, the use of reservoirs of molecules to maintain concentrations of key molecular species, and negative feedback are the primary known mechanisms for robust homeostatic regulation. To our knowledge, however, the fundamental principles behind their combined effect have not been elucidated. Here, we study the interplay between buffering and negative feedback in the context of cellular homeostasis. We show that negative feedback counteracts slow-changing disturbances, whereas buffering counteracts fast-changing disturbances. Furthermore, feedback and buffering have limitations that create trade-offs for regulation: instability in the case of feedback and molecular noise in the case of buffering. However, because buffering stabilizes feedback and feedback attenuates noise from slower-acting buffering, their combined effect on homeostasis can be synergistic. These effects can be explained within a traditional control theory framework and are consistent with experimental observations of both ATP homeostasis and pH regulation in vivo. These principles are critical for studying robustness and homeostasis in biology and biotechnology. |
| first_indexed | 2024-03-07T03:49:14Z |
| format | Journal article |
| id | oxford-uuid:c0a54a6e-f8ef-4457-9992-0e4989db2a44 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T03:49:14Z |
| publishDate | 2017 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:c0a54a6e-f8ef-4457-9992-0e4989db2a442022-03-27T05:55:48ZThe Interplay between Feedback and Buffering in Cellular HomeostasisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c0a54a6e-f8ef-4457-9992-0e4989db2a44EnglishSymplectic Elements at OxfordElsevier2017Hancock, EAng, JPapachristodoulou, AStan, GBuffering, the use of reservoirs of molecules to maintain concentrations of key molecular species, and negative feedback are the primary known mechanisms for robust homeostatic regulation. To our knowledge, however, the fundamental principles behind their combined effect have not been elucidated. Here, we study the interplay between buffering and negative feedback in the context of cellular homeostasis. We show that negative feedback counteracts slow-changing disturbances, whereas buffering counteracts fast-changing disturbances. Furthermore, feedback and buffering have limitations that create trade-offs for regulation: instability in the case of feedback and molecular noise in the case of buffering. However, because buffering stabilizes feedback and feedback attenuates noise from slower-acting buffering, their combined effect on homeostasis can be synergistic. These effects can be explained within a traditional control theory framework and are consistent with experimental observations of both ATP homeostasis and pH regulation in vivo. These principles are critical for studying robustness and homeostasis in biology and biotechnology. |
| spellingShingle | Hancock, E Ang, J Papachristodoulou, A Stan, G The Interplay between Feedback and Buffering in Cellular Homeostasis |
| title | The Interplay between Feedback and Buffering in Cellular Homeostasis |
| title_full | The Interplay between Feedback and Buffering in Cellular Homeostasis |
| title_fullStr | The Interplay between Feedback and Buffering in Cellular Homeostasis |
| title_full_unstemmed | The Interplay between Feedback and Buffering in Cellular Homeostasis |
| title_short | The Interplay between Feedback and Buffering in Cellular Homeostasis |
| title_sort | interplay between feedback and buffering in cellular homeostasis |
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