{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T10:55:19Z","timestamp":1767178519309,"version":"build-2238731810"},"update-to":[{"DOI":"10.1371\/journal.pcbi.1013746","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000}}],"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T00:00:00Z","timestamp":1764806400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM137758"],"award-info":[{"award-number":["R35GM137758"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R35GM142584"],"award-info":[{"award-number":["R35GM142584"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","award":["2027108"],"award-info":[{"award-number":["2027108"]}],"id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000861","name":"Burroughs Wellcome Fund","doi-asserted-by":"publisher","award":["Career Award at the Scientific Interface"],"award-info":[{"award-number":["Career Award at the Scientific Interface"]}],"id":[{"id":"10.13039\/100000861","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"abstract":"<jats:p>\n                    Microbes of nearly every species can form biofilms, communities of cells bound together by a self-produced matrix. It is not understood how variation at the cellular level impacts putatively beneficial, colony-level behaviors, such as cell-to-cell signaling. Here we investigate this problem with an agent-based computational model of metabolically driven electrochemical signaling in\n                    <jats:italic>Bacillus subtilis<\/jats:italic>\n                    biofilms. In this process, glutamate-starved interior cells release potassium, triggering a depolarizing wave that spreads to exterior cells and limits their glutamate uptake. More nutrients diffuse to the interior, temporarily reducing glutamate stress and leading to oscillations. In our model, each cell has a membrane potential coupled to metabolism. As a simulated biofilm grows, collective membrane potential oscillations arise spontaneously as cells deplete nutrients and trigger potassium release, reproducing experimental observations. We further validate our model by comparing spatial signaling patterns and cellular signaling rates with those observed experimentally. By oscillating external glutamate and potassium, we find that biofilms synchronize to external potassium, providing a potential mechanism for previously observed oscillation synchronization. By tracking cellular glutamate concentrations, we find that oscillations evenly distribute nutrients in space: non-oscillating biofilms have an external layer of well-fed cells surrounding a starved core, whereas oscillating biofilms exhibit a relatively uniform distribution of glutamate. Our work shows the potential of agent-based models to connect cellular properties to collective phenomena and facilitates studies of how inheritance of cellular traits can affect the evolution of group behaviors.\n                  <\/jats:p>","DOI":"10.1371\/journal.pcbi.1013746","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T19:01:51Z","timestamp":1764874911000},"page":"e1013746","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["An agent-based model of metabolic signaling oscillations in Bacillus subtilis biofilms"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2992-8323","authenticated-orcid":true,"given":"Obadiah J.","family":"Mulder","sequence":"first","affiliation":[]},{"given":"Maya","family":"Peters Kostman","sequence":"additional","affiliation":[]},{"given":"Abdulrahmen","family":"Almodaimegh","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8773-2906","authenticated-orcid":true,"given":"Michael D.","family":"Edge","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5660-0246","authenticated-orcid":true,"given":"Joseph W.","family":"Larkin","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2025,12,4]]},"reference":[{"issue":"4","key":"pcbi.1013746.ref001","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1038\/s41579-019-0158-9","article-title":"Bacteria and archaea on Earth and their abundance in biofilms","volume":"17","author":"H-C Flemming","year":"2019","journal-title":"Nat Rev Microbiol."},{"issue":"1","key":"pcbi.1013746.ref002","doi-asserted-by":"crossref","first-page":"20","DOI":"10.1016\/j.tim.2004.11.006","article-title":"Biofilms: the matrix revisited","volume":"13","author":"SS Branda","year":"2005","journal-title":"Trends Microbiol."},{"issue":"12","key":"pcbi.1013746.ref003","doi-asserted-by":"crossref","DOI":"10.1016\/j.cub.2018.04.046","article-title":"Division of labor during biofilm matrix production","volume":"28","author":"A Drago\u0161","year":"2018","journal-title":"Curr Biol."},{"issue":"9","key":"pcbi.1013746.ref004","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1038\/s41579-021-00540-9","article-title":"Bacillus subtilis biofilm formation and social interactions","volume":"19","author":"S Arnaouteli","year":"2021","journal-title":"Nat Rev Microbiol."},{"issue":"2","key":"pcbi.1013746.ref005","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1111\/j.1574-6968.2004.tb09643.x","article-title":"What drives bacteria to produce a biofilm?","volume":"236","author":"KK Jefferson","year":"2004","journal-title":"FEMS Microbiol Lett."},{"issue":"1","key":"pcbi.1013746.ref006","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1574-6976.2008.00150.x","article-title":"The sociobiology of biofilms","volume":"33","author":"CD Nadell","year":"2009","journal-title":"FEMS Microbiol Rev."},{"issue":"3","key":"pcbi.1013746.ref007","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1128\/microbiolspec.MB-0010-2014","article-title":"Antimicrobial tolerance in biofilms","volume":"3","author":"PS Stewart","year":"2015","journal-title":"Microbiology Spectrum."},{"key":"pcbi.1013746.ref008","doi-asserted-by":"crossref","unstructured":"Lewis K, Spoering AL, Kaldalu N, Keren I, Shah D. 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