An Artificial Tissue Homeostasis Circuit Designed via Analog Circuit Techniques
Tissue homeostasis (feedback control) is an important mechanism that regulates the population of different cell types within a tissue. In type-1 diabetes, auto-immune attack and consequent death of pancreatic β cells result in the failure of homeostasis and loss of organ function. Synthetically engi...
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| Format: | Article |
| Language: | English |
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Institute of Electrical and Electronics Engineers (IEEE)
2021
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| Online Access: | https://hdl.handle.net/1721.1/129772 |
| _version_ | 1811070374283051008 |
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| author | Teo, Jonathan Jin Yuan. Weiss, Ron Sarpeshkar, Rahul |
| author2 | Massachusetts Institute of Technology. Computational and Systems Biology Program |
| author_facet | Massachusetts Institute of Technology. Computational and Systems Biology Program Teo, Jonathan Jin Yuan. Weiss, Ron Sarpeshkar, Rahul |
| author_sort | Teo, Jonathan Jin Yuan. |
| collection | MIT |
| description | Tissue homeostasis (feedback control) is an important mechanism that regulates the population of different cell types within a tissue. In type-1 diabetes, auto-immune attack and consequent death of pancreatic β cells result in the failure of homeostasis and loss of organ function. Synthetically engineered adult stem cells with homeostatic control based on digital logic have been proposed as a solution for regenerating β cells. Such previously proposed homeostatic control circuits have thus far been unable to reliably control both stem-cell proliferation and stem-cell differentiation. Using analog circuits and feedback systems analysis, we have designed an in silico circuit that performs homeostatic control by utilizing a novel scheme with both symmetric and asymmetric division of stem cells. The use of a variety of feedback systems analysis techniques, which is common in analog circuit design, including root-locus techniques, Bode plots of feedback-loop frequency response, compensation techniques for improving stability, and robustness analysis help us choose design parameters to meet desirable specifications. For example, we show that lead compensation in analog circuits instantiated as an incoherent feed-forward loop in the biological circuit improves stability, whereas simultaneously reducing steady-state tracking error. Our symmetric and asymmetric division scheme also improves phase margin in the feedback loop, and thus improves robustness. This paper could be useful in porting an analog-circuit design framework to synthetic biological applications of the future. |
| first_indexed | 2024-09-23T08:34:57Z |
| format | Article |
| id | mit-1721.1/129772 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T08:34:57Z |
| publishDate | 2021 |
| publisher | Institute of Electrical and Electronics Engineers (IEEE) |
| record_format | dspace |
| spelling | mit-1721.1/1297722022-09-23T13:03:39Z An Artificial Tissue Homeostasis Circuit Designed via Analog Circuit Techniques Teo, Jonathan Jin Yuan. Weiss, Ron Sarpeshkar, Rahul Massachusetts Institute of Technology. Computational and Systems Biology Program Tissue homeostasis (feedback control) is an important mechanism that regulates the population of different cell types within a tissue. In type-1 diabetes, auto-immune attack and consequent death of pancreatic β cells result in the failure of homeostasis and loss of organ function. Synthetically engineered adult stem cells with homeostatic control based on digital logic have been proposed as a solution for regenerating β cells. Such previously proposed homeostatic control circuits have thus far been unable to reliably control both stem-cell proliferation and stem-cell differentiation. Using analog circuits and feedback systems analysis, we have designed an in silico circuit that performs homeostatic control by utilizing a novel scheme with both symmetric and asymmetric division of stem cells. The use of a variety of feedback systems analysis techniques, which is common in analog circuit design, including root-locus techniques, Bode plots of feedback-loop frequency response, compensation techniques for improving stability, and robustness analysis help us choose design parameters to meet desirable specifications. For example, we show that lead compensation in analog circuits instantiated as an incoherent feed-forward loop in the biological circuit improves stability, whereas simultaneously reducing steady-state tracking error. Our symmetric and asymmetric division scheme also improves phase margin in the feedback loop, and thus improves robustness. This paper could be useful in porting an analog-circuit design framework to synthetic biological applications of the future. NIH (R01 Award GM123032) AFSOR (Grant FA955018-1-0467) Agency for Science, Technology and Research (Fellowship) 2021-02-16T19:41:42Z 2021-02-16T19:41:42Z 2019-06 2020-06-19T17:36:08Z Article http://purl.org/eprint/type/JournalArticle 1932-4545 1940-9990 https://hdl.handle.net/1721.1/129772 Teo, Jonathan J.Y. et al. " An artificial tissue homeostasis circuit designed via analog circuit techniques" IEEE Transactions on Biomedical Circuits and Systems 13, 3 (June 2019): 540-553. © 2007-2012 IEEE. en 10.1109/TBCAS.2019.2907074 IEEE Transactions on Biomedical Circuits and Systems Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Institute of Electrical and Electronics Engineers (IEEE) PMC |
| spellingShingle | Teo, Jonathan Jin Yuan. Weiss, Ron Sarpeshkar, Rahul An Artificial Tissue Homeostasis Circuit Designed via Analog Circuit Techniques |
| title | An Artificial Tissue Homeostasis Circuit Designed via Analog Circuit Techniques |
| title_full | An Artificial Tissue Homeostasis Circuit Designed via Analog Circuit Techniques |
| title_fullStr | An Artificial Tissue Homeostasis Circuit Designed via Analog Circuit Techniques |
| title_full_unstemmed | An Artificial Tissue Homeostasis Circuit Designed via Analog Circuit Techniques |
| title_short | An Artificial Tissue Homeostasis Circuit Designed via Analog Circuit Techniques |
| title_sort | artificial tissue homeostasis circuit designed via analog circuit techniques |
| url | https://hdl.handle.net/1721.1/129772 |
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