A deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acids

Hdl Handle:
http://hdl.handle.net/10034/618346
Title:
A deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acids
Authors:
Kilner, Josephine; Corfe, Bernard M.; Mc Auley, Mark T.; Wilkinson, Stephen J.
Abstract:
Short chain fatty acids (SCFA), principally acetate, propionate, butyrate and valerate, are produced in pharmacologically relevant concentrations by the gut microbiome. Investigations indicate that they exert beneficial effects on colon epithelia. There is increasing interest in whether different SCFAs have distinct functions which may be exploited for prevention or treatment of colonic diseases including colorectal cancer (CRC), inflammatory bowel disease and obesity. Based on experimental evidence, we hypothe-sised that odd-chain SCFAs may possess anti-mitotic capabilities in colon cancer cells by disrupting microtubule (MT) structural integrity via dysregulation of b-tubulin isotypes. MT dynamic instability is an essential characteristic of MT cellular activity. We report a minimal deterministic model that takes a novel approach to explore the hypothesised pathway by triggering spontaneous oscillations to represent MT dynamic behaviour. The dynamicity parameters in silico were compared to those reported in vitro.Simulations of untreated and butyrate (even-chain length) treated cells reflected MT behaviour in interphase or untreated control cells. The propionate and valerate (odd-chain length) simulations displayed increased catastrophe frequencies and longer periods of MT-fibre shrinkage. Their enhanced dynamicity wasdissimilar to that observed in mitotic cells, but parallel to that induced by MT-destabilisation treatments.Antimicrotubule drugs act through upward or downward modulation of MT dynamic instability. Our computational modelling suggests that metabolic engineering of the microbiome may facilitate managing CRC risk by predicting outcomes of SCFA treatments in combination with AMDs
Affiliation:
University of Sheffield; University of Chester
Citation:
Kilner, J., Corfe, B. M., Mc Auley, M. T., & Wilkinson, S. J. (2016). A deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acids. Molecular Biosystems, 12, 93-113. DOI: 10.1039/c5mb00211g
Publisher:
Royal Society of Chemistry
Journal:
Molecular Biosystems
Publication Date:
1-Jan-2016
URI:
http://hdl.handle.net/10034/618346
DOI:
10.1039/c5mb00211g
Additional Links:
http://pubs.rsc.org/en/Content/ArticleLanding/2016/MB/C5MB00211G#!divAbstract
Type:
Article
Language:
en
EISSN:
1742-2051
Appears in Collections:
Chemical Engineering

Full metadata record

DC FieldValue Language
dc.contributor.authorKilner, Josephineen
dc.contributor.authorCorfe, Bernard M.en
dc.contributor.authorMc Auley, Mark T.en
dc.contributor.authorWilkinson, Stephen J.en
dc.date.accessioned2016-08-11T16:32:36Z-
dc.date.available2016-08-11T16:32:36Z-
dc.date.issued2016-01-01-
dc.identifier.citationKilner, J., Corfe, B. M., Mc Auley, M. T., & Wilkinson, S. J. (2016). A deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acids. Molecular Biosystems, 12, 93-113. DOI: 10.1039/c5mb00211gen
dc.identifier.doi10.1039/c5mb00211g-
dc.identifier.urihttp://hdl.handle.net/10034/618346-
dc.description.abstractShort chain fatty acids (SCFA), principally acetate, propionate, butyrate and valerate, are produced in pharmacologically relevant concentrations by the gut microbiome. Investigations indicate that they exert beneficial effects on colon epithelia. There is increasing interest in whether different SCFAs have distinct functions which may be exploited for prevention or treatment of colonic diseases including colorectal cancer (CRC), inflammatory bowel disease and obesity. Based on experimental evidence, we hypothe-sised that odd-chain SCFAs may possess anti-mitotic capabilities in colon cancer cells by disrupting microtubule (MT) structural integrity via dysregulation of b-tubulin isotypes. MT dynamic instability is an essential characteristic of MT cellular activity. We report a minimal deterministic model that takes a novel approach to explore the hypothesised pathway by triggering spontaneous oscillations to represent MT dynamic behaviour. The dynamicity parameters in silico were compared to those reported in vitro.Simulations of untreated and butyrate (even-chain length) treated cells reflected MT behaviour in interphase or untreated control cells. The propionate and valerate (odd-chain length) simulations displayed increased catastrophe frequencies and longer periods of MT-fibre shrinkage. Their enhanced dynamicity wasdissimilar to that observed in mitotic cells, but parallel to that induced by MT-destabilisation treatments.Antimicrotubule drugs act through upward or downward modulation of MT dynamic instability. Our computational modelling suggests that metabolic engineering of the microbiome may facilitate managing CRC risk by predicting outcomes of SCFA treatments in combination with AMDsen
dc.language.isoenen
dc.publisherRoyal Society of Chemistryen
dc.relation.urlhttp://pubs.rsc.org/en/Content/ArticleLanding/2016/MB/C5MB00211G#!divAbstracten
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectFatty acidsen
dc.subjectCanceren
dc.titleA deterministic oscillatory model of microtubule growth and shrinkage for differential actions of short chain fatty acidsen
dc.typeArticleen
dc.identifier.eissn1742-2051-
dc.contributor.departmentUniversity of Sheffield; University of Chesteren
dc.identifier.journalMolecular Biosystemsen
dc.date.accepted2015-11-09-
or.grant.openaccessYesen
rioxxterms.funderEPSRCen
rioxxterms.identifier.projectEP/E036252/1en
rioxxterms.versionSMURen
rioxxterms.licenseref.startdate2016-11-09-
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