{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:28:48Z","timestamp":1789658928850,"version":"4.0.1"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1014729","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000}}],"reference-count":79,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T00:00:00Z","timestamp":1788307200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education, Government of India","award":["PMRF ID: 3003659"],"award-info":[{"award-number":["PMRF ID: 3003659"]}],"id":[{"id":"https:\/\/ror.org\/036h6g940","id-type":"ROR","asserted-by":"crossref"}]},{"name":"SERB India","award":["CRG\/2022\/001127"],"award-info":[{"award-number":["CRG\/2022\/001127"]}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"\n E. coli<\/jats:italic>\n relies on the heat shock response (HSR) to preserve protein homeostasis under stress, through three feedback modules: feedforward translational control, chaperone-mediated sequestration and targeted degradation. Although previous studies have highlighted how this layered architecture ensures rapid and robust protection compared to simpler designs, not much attention is paid to how these modules interact. Moreover, how do interactions among the three modules balance performance trade-offs, where gains in one module may come at the expense of another, yet together yield an optimal overall response? We address this using a mathematical model that integrates protein folding with\n \n \n \n \n \n \n \u03c3<\/mml:mi>\n \n 32<\/mml:mn>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n regulation. We show that the feedback modules both cooperate and compete, giving rise to nonmonotonic dynamics that govern HSR performance. Specifically, increasing feedforward strength does accelerate response, but beyond a threshold, despite increasing chaperone levels, it paradoxically slows recovery. Similarly, while sequestration enhances relative chaperone production and per-chaperone efficiency, when excessive, it traps\n \n \n \n \n \n \n \u03c3<\/mml:mi>\n \n 32<\/mml:mn>\n <\/mml:mrow>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:math>\n <\/jats:alternatives>\n <\/jats:inline-formula>\n in inactive complexes, prolonging recovery and delaying shutdown. Mapping the parameter space reveals regimes of synergy as well as trade-offs between speed and efficiency, with wild-type parameters lying near the optimal region. These results reveal design principles that produces a robust and efficient heat shock response.\n <\/jats:p>","DOI":"10.1371\/journal.pcbi.1014729","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T17:47:38Z","timestamp":1788371258000},"page":"e1014729","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Synergies and trade-offs in the heat shock response mechanism"],"prefix":"10.1371","volume":"22","author":[{"given":"Rupal","family":"Chauhan","sequence":"first","affiliation":[{"name":"Indian Institute of Technology Jammu","place":["Jammu, India"],"department":["Department of Physics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biswajit","family":"Das","sequence":"additional","affiliation":[{"name":"Amrita School of Artificial Intelligence, Amrita Vishwa Vidyapeetham","place":["Coimbatore, India"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2819-1668","authenticated-orcid":true,"given":"Ajeet K.","family":"Sharma","sequence":"additional","affiliation":[{"name":"Indian Institute of Technology Jammu","place":["Jammu, India"],"department":["Department of Physics"]},{"name":"Indian Institute of Technology Jammu","place":["Jammu, India"],"department":["Department of Biosciences and Bioengineering"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,9,2]]},"reference":[{"key":"pcbi.1014729.ref001","volume-title":"Protein function. 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