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dc.contributor.authorWu, Shan
dc.contributor.authorWells, Alan
dc.contributor.authorGriffith, Linda G.
dc.contributor.authorLauffenburger, Douglas A.
dc.date.accessioned2015-03-04T19:41:01Z
dc.date.available2015-03-04T19:41:01Z
dc.date.issued2011-10
dc.date.submitted2011-06
dc.identifier.issn01429612
dc.identifier.urihttp://hdl.handle.net/1721.1/95816
dc.description.abstractBiomimetic scaffolds have been proposed as a means to facilitate tissue regeneration by multi-potent stromal cells (MSCs). Effective scaffold colonization requires a control of multiple MSC responses including survival, proliferation, differentiation, and migration. As MSC migration is relatively unstudied in this context, we present here a multi-level approach to its understanding and control, integratively tuning cell speed and directional persistence to achieve maximal mean free path (MFP) of migration. This approach employs data-driven computational modeling to ascertain small molecule drug treatments that can enhance MFP on a given materials substratum. Using poly(methyl methacrylate)-graft-poly(ethylene oxide) polymer surfaces tethered with epidermal growth factor (tEGF) and systematically adsorbed with fibronectin, vitronectin, or collagen-I to present hTERT-immortalized human MSCs with growth factor and extracellular matrix cues, we measured cell motility properties along with signaling activities of EGFR, ERK, Akt, and FAK on 19 different substrate conditions. Speed was consistent on collagen/tEGF substrates, but low associated directional persistence limited MFP. Decision tree modeling successfully predicted that ERK inhibition should enhance MFP on collagen/tEGF substrates by increasing persistence. Thus, we demonstrated a two-tiered approach to control MSC migration: materials-based “coarse-graining” complemented by small molecule “fine-tuning”.en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant R01-DE019523)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH Cell Migration Consortium U54-GM064346)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant R01-GM018336)en_US
dc.description.sponsorshipNational Institutes of Health (U.S.) (NIH grant R01-DE019523)en_US
dc.language.isoen_US
dc.publisherElsevier B.V.en_US
dc.relation.isversionofhttp://dx.doi.org/10.1016/j.biomaterials.2011.06.050en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/en_US
dc.sourceElsevieren_US
dc.titleControlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modelingen_US
dc.typeArticleen_US
dc.identifier.citationWu, Shan, Alan Wells, Linda G. Griffith, and Douglas A. Lauffenburger. “Controlling Multipotent Stromal Cell Migration by Integrating ‘course-Graining’ Materials and ‘fine-Tuning’ Small Molecules via Decision Tree Signal-Response Modeling.” Biomaterials 32, no. 30 (October 2011): 7524–7531. © 2011 Elsevier Ltd.en_US
dc.contributor.departmentMassachusetts Institute of Technology. Department of Biological Engineeringen_US
dc.contributor.mitauthorWu, Shanen_US
dc.contributor.mitauthorGriffith, Linda G.en_US
dc.contributor.mitauthorLauffenburger, Douglas A.en_US
dc.relation.journalBiomaterialsen_US
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dspace.orderedauthorsWu, Shan; Wells, Alan; Griffith, Linda G.; Lauffenburger, Douglas A.en_US
dc.identifier.orcidhttps://orcid.org/0000-0002-1801-5548
mit.licensePUBLISHER_CCen_US


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