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dc.contributor.authorBradshaw, Mark J.en_US
dc.contributor.authorCheung, Man C.en_US
dc.contributor.authorEhrlich, Daniel J.en_US
dc.contributor.authorSmith, Michael L.en_US
dc.coverage.spatialUnited Statesen_US
dc.date2012-11-02
dc.date.accessioned2018-07-18T12:51:22Z
dc.date.available2018-07-18T12:51:22Z
dc.date.issued2012
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/23300425
dc.identifier.citationBradshaw MJ, Cheung MC, Ehrlich DJ, Smith ML (2012) Using Molecular Mechanics to Predict Bulk Material Properties of Fibronectin Fibers. PLoS Comput Biol 8(12): e1002845. https://doi.org/10.1371/journal.pcbi.1002845
dc.identifier.issn1553-7358
dc.identifier.urihttps://hdl.handle.net/2144/29970
dc.description.abstractThe structural proteins of the extracellular matrix (ECM) form fibers with finely tuned mechanical properties matched to the time scales of cell traction forces. Several proteins such as fibronectin (Fn) and fibrin undergo molecular conformational changes that extend the proteins and are believed to be a major contributor to the extensibility of bulk fibers. The dynamics of these conformational changes have been thoroughly explored since the advent of single molecule force spectroscopy and molecular dynamics simulations but remarkably, these data have not been rigorously applied to the understanding of the time dependent mechanics of bulk ECM fibers. Using measurements of protein density within fibers, we have examined the influence of dynamic molecular conformational changes and the intermolecular arrangement of Fn within fibers on the bulk mechanical properties of Fn fibers. Fibers were simulated as molecular strands with architectures that promote either equal or disparate molecular loading under conditions of constant extension rate. Measurements of protein concentration within micron scale fibers using deep ultraviolet transmission microscopy allowed the simulations to be scaled appropriately for comparison to in vitro measurements of fiber mechanics as well as providing estimates of fiber porosity and water content, suggesting Fn fibers are approximately 75% solute. Comparing the properties predicted by single molecule measurements to in vitro measurements of Fn fibers showed that domain unfolding is sufficient to predict the high extensibility and nonlinear stiffness of Fn fibers with surprising accuracy, with disparately loaded fibers providing the best fit to experiment. This work shows the promise of this microstructural modeling approach for understanding Fn fiber properties, which is generally applicable to other ECM fibers, and could be further expanded to tissue scale by incorporating these simulated fibers into three dimensional network models.en_US
dc.format.extente1002845en_US
dc.languageeng
dc.relation.ispartofPLoS Comput Biol
dc.rightsCopyright: © 2012 Bradshaw et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectScience & technologyen_US
dc.subjectLife sciences & biomedicineen_US
dc.subjectBiochemical research methodsen_US
dc.subjectMathematical & computational biologyen_US
dc.subjectBiochemistry & molecular biologyen_US
dc.subjectExtracellular matrix proteinsen_US
dc.subjectHuman fibroblast culturesen_US
dc.subjectFibrin fibersen_US
dc.subjectStretching fibronectinen_US
dc.subjectIII modulesen_US
dc.subjectPlasmaen_US
dc.subjectExtracellular matrixen_US
dc.subjectFibronectinsen_US
dc.subjectMicroscopyen_US
dc.subjectModels, molecularen_US
dc.subjectProtein conformationen_US
dc.subjectProtein denaturationen_US
dc.subjectBiological sciencesen_US
dc.subjectInformation and computing sciencesen_US
dc.subjectMathematical sciencesen_US
dc.subjectBioinformaticsen_US
dc.titleUsing molecular mechanics to predict bulk material properties of fibronectin fibersen_US
dc.typeArticleen_US
dc.identifier.doi10.1371/journal.pcbi.1002845
pubs.elements-sourcepubmeden_US
pubs.notesEmbargo: Not knownen_US
pubs.organisational-groupBoston Universityen_US
pubs.organisational-groupBoston University, College of Engineeringen_US
pubs.organisational-groupBoston University, College of Engineering, Department of Biomedical Engineeringen_US
pubs.publication-statusPublisheden_US


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Copyright: © 2012 Bradshaw et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Except where otherwise noted, this item's license is described as Copyright: © 2012 Bradshaw et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.