A molecular dynamics approach towards evaluating osmotic and thermal stress in the extracellular environment

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dc.citation.journalTitleInternational Journal of Hyperthermia
dc.contributor.authorFuentes, David
dc.contributor.authorMuñoz, Nina M.
dc.contributor.authorGuo, Chunxiao
dc.contributor.authorPolak, Urzsula
dc.contributor.authorMinhaj, Adeeb A.
dc.contributor.authorAllen, William J.
dc.contributor.authorGustin, Michael C.
dc.contributor.authorCressman, Erik N.K.
dc.date.accessioned2019-01-08T15:37:45Z
dc.date.available2019-01-08T15:37:45Z
dc.date.issued2018
dc.description.abstractOBJECTIVE: A molecular dynamics approach to understanding fundamental mechanisms of combined thermal and osmotic stress induced by thermochemical ablation (TCA) is presented. METHODS: Structural models of fibronectin and fibronectin bound to its integrin receptor provide idealized models for the effects of thermal and osmotic stress in the extracellular matrix. Fibronectin binding to integrin is known to facilitate cell survival. The extracellular environment produced by TCA at the lesion boundary was modelled at 37 °C and 43 °C with added sodium chloride (NaCl) concentrations (0, 40, 80, 160, and 320 mM). Atomistic simulations of solvated proteins were performed using the GROMOS96 force field and TIP3P water model. Computational results were compared with the results of viability studies of human hepatocellular carcinoma (HCC) cell lines HepG2 and Hep3B under matching thermal and osmotic experimental conditions. RESULTS: Cell viability was inversely correlated with hyperthermal and hyperosmotic stresses. Added NaCl concentrations were correlated with a root mean square fluctuation increase of the fibronectin arginylglycylaspartic acid (RGD) binding domain. Computed interaction coefficients demonstrate preferential hydration of the protein model and are correlated with salt-induced strengthening of hydrophobic interactions. Under the combined hyperthermal and hyperosmotic stress conditions (43 °C and 320 mM added NaCl), the free energy change required for fibronectin binding to integrin was less favorable than that for binding under control conditions (37 °C and 0 mM added NaCl). CONCLUSION: Results quantify multiple measures of structural changes as a function of temperature increase and addition of NaCl to the solution. Correlations between cell viability and stability measures suggest that protein aggregates, non-functional proteins, and less favorable cell attachment conditions have a role in TCA-induced cell stress.
dc.identifier.citationFuentes, David, Muñoz, Nina M., Guo, Chunxiao, et al.. "A molecular dynamics approach towards evaluating osmotic and thermal stress in the extracellular environment." <i>International Journal of Hyperthermia,</i> (2018) Taylor & Francis: https://doi.org/10.1080/02656736.2018.1512161.
dc.identifier.digitalmolecular-dynamics-approach
dc.identifier.doihttps://doi.org/10.1080/02656736.2018.1512161
dc.identifier.urihttps://hdl.handle.net/1911/104981
dc.language.isoeng
dc.publisherTaylor & Francis
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subject.keywordHyperthermia
dc.subject.keywordmolecular dynamics
dc.subject.keywordthermochemical ablation
dc.titleA molecular dynamics approach towards evaluating osmotic and thermal stress in the extracellular environment
dc.typeJournal article
dc.type.dcmiText
dc.type.publicationpublisher version
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