Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling
Biomimetic 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 un...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | en_US |
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Elsevier B.V.
2015
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| Online Access: | http://hdl.handle.net/1721.1/95816 https://orcid.org/0000-0002-1801-5548 |
| _version_ | 1826205030166822912 |
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| author | Wu, Shan Wells, Alan Griffith, Linda G. Lauffenburger, Douglas A. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Wu, Shan Wells, Alan Griffith, Linda G. Lauffenburger, Douglas A. |
| author_sort | Wu, Shan |
| collection | MIT |
| description | Biomimetic 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”. |
| first_indexed | 2024-09-23T13:05:39Z |
| format | Article |
| id | mit-1721.1/95816 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:05:39Z |
| publishDate | 2015 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/958162022-10-01T12:57:59Z Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling Wu, Shan Wells, Alan Griffith, Linda G. Lauffenburger, Douglas A. Massachusetts Institute of Technology. Department of Biological Engineering Wu, Shan Griffith, Linda G. Lauffenburger, Douglas A. Biomimetic 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”. National Institutes of Health (U.S.) (NIH grant R01-DE019523) National Institutes of Health (U.S.) (NIH Cell Migration Consortium U54-GM064346) National Institutes of Health (U.S.) (NIH grant R01-GM018336) National Institutes of Health (U.S.) (NIH grant R01-DE019523) 2015-03-04T19:41:01Z 2015-03-04T19:41:01Z 2011-10 2011-06 Article http://purl.org/eprint/type/JournalArticle 01429612 http://hdl.handle.net/1721.1/95816 Wu, 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. https://orcid.org/0000-0002-1801-5548 en_US http://dx.doi.org/10.1016/j.biomaterials.2011.06.050 Biomaterials Creative Commons Attribution http://creativecommons.org/licenses/by-nc-nd/3.0/ application/pdf Elsevier B.V. Elsevier |
| spellingShingle | Wu, Shan Wells, Alan Griffith, Linda G. Lauffenburger, Douglas A. Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling |
| title | Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling |
| title_full | Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling |
| title_fullStr | Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling |
| title_full_unstemmed | Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling |
| title_short | Controlling multipotent stromal cell migration by integrating “course-graining” materials and “fine-tuning” small molecules via decision tree signal-response modeling |
| title_sort | controlling multipotent stromal cell migration by integrating course graining materials and fine tuning small molecules via decision tree signal response modeling |
| url | http://hdl.handle.net/1721.1/95816 https://orcid.org/0000-0002-1801-5548 |
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