Mechanotransduction of fluid stresses governs 3D cell migration
Solid tumors are characterized by high interstitial fluid pressure, which drives fluid efflux from the tumor core. Tumor-associated interstitial flow (IF) at a rate of ∼3 µm/s has been shown to induce cell migration in the upstream direction (rheotaxis). However, the molecular biophysical mechanism...
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2014
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| Online Access: | http://hdl.handle.net/1721.1/90327 https://orcid.org/0000-0003-2728-0746 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1811085328532897792 |
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| author | Polacheck, William J. German, Alexandra E. Mammoto, Akiko Ingber, Donald E. Kamm, Roger Dale |
| author2 | Harvard University--MIT Division of Health Sciences and Technology |
| author_facet | Harvard University--MIT Division of Health Sciences and Technology Polacheck, William J. German, Alexandra E. Mammoto, Akiko Ingber, Donald E. Kamm, Roger Dale |
| author_sort | Polacheck, William J. |
| collection | MIT |
| description | Solid tumors are characterized by high interstitial fluid pressure, which drives fluid efflux from the tumor core. Tumor-associated interstitial flow (IF) at a rate of ∼3 µm/s has been shown to induce cell migration in the upstream direction (rheotaxis). However, the molecular biophysical mechanism that underlies upstream cell polarization and rheotaxis remains unclear. We developed a microfluidic platform to investigate the effects of IF fluid stresses imparted on cells embedded within a collagen type I hydrogel, and we demonstrate that IF stresses result in a transcellular gradient in β1-integrin activation with vinculin, focal adhesion kinase (FAK), FAK[superscript PY397], F actin, and paxillin-dependent protrusion formation localizing to the upstream side of the cell, where matrix adhesions are under maximum tension. This previously unknown mechanism is the result of a force balance between fluid drag on the cell and matrix adhesion tension and is therefore a fundamental, but previously unknown, stimulus for directing cell movement within porous extracellular matrix. |
| first_indexed | 2024-09-23T13:07:11Z |
| format | Article |
| id | mit-1721.1/90327 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T13:07:11Z |
| publishDate | 2014 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/903272022-09-28T12:05:26Z Mechanotransduction of fluid stresses governs 3D cell migration Polacheck, William J. German, Alexandra E. Mammoto, Akiko Ingber, Donald E. Kamm, Roger Dale Harvard University--MIT Division of Health Sciences and Technology Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Polacheck, William J. German, Alexandra E. Kamm, Roger Dale Solid tumors are characterized by high interstitial fluid pressure, which drives fluid efflux from the tumor core. Tumor-associated interstitial flow (IF) at a rate of ∼3 µm/s has been shown to induce cell migration in the upstream direction (rheotaxis). However, the molecular biophysical mechanism that underlies upstream cell polarization and rheotaxis remains unclear. We developed a microfluidic platform to investigate the effects of IF fluid stresses imparted on cells embedded within a collagen type I hydrogel, and we demonstrate that IF stresses result in a transcellular gradient in β1-integrin activation with vinculin, focal adhesion kinase (FAK), FAK[superscript PY397], F actin, and paxillin-dependent protrusion formation localizing to the upstream side of the cell, where matrix adhesions are under maximum tension. This previously unknown mechanism is the result of a force balance between fluid drag on the cell and matrix adhesion tension and is therefore a fundamental, but previously unknown, stimulus for directing cell movement within porous extracellular matrix. National Science Foundation (U.S.). Graduate Research Fellowship 2014-09-24T19:34:36Z 2014-09-24T19:34:36Z 2014-02 2013-09 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/90327 Polacheck, W. J., A. E. German, A. Mammoto, D. E. Ingber, and R. D. Kamm. “Mechanotransduction of Fluid Stresses Governs 3D Cell Migration.” Proceedings of the National Academy of Sciences 111, no. 7 (February 3, 2014): 2447–2452. https://orcid.org/0000-0003-2728-0746 https://orcid.org/0000-0002-7232-304X en_US http://dx.doi.org/10.1073/pnas.1316848111 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences (U.S.) |
| spellingShingle | Polacheck, William J. German, Alexandra E. Mammoto, Akiko Ingber, Donald E. Kamm, Roger Dale Mechanotransduction of fluid stresses governs 3D cell migration |
| title | Mechanotransduction of fluid stresses governs 3D cell migration |
| title_full | Mechanotransduction of fluid stresses governs 3D cell migration |
| title_fullStr | Mechanotransduction of fluid stresses governs 3D cell migration |
| title_full_unstemmed | Mechanotransduction of fluid stresses governs 3D cell migration |
| title_short | Mechanotransduction of fluid stresses governs 3D cell migration |
| title_sort | mechanotransduction of fluid stresses governs 3d cell migration |
| url | http://hdl.handle.net/1721.1/90327 https://orcid.org/0000-0003-2728-0746 https://orcid.org/0000-0002-7232-304X |
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