Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis
Development of tissues in vitro with dimensions larger than 150 to 200μm requires the presence of a functional vascular network. Therefore, we have studied capillary morphogenesis under controlled biological and biophysical conditions with the aim of promoting vascular structures in tissue construct...
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| Format: | Article |
| Language: | en_US |
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Mary Ann Liebert, Inc.
2010
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| Online Access: | http://hdl.handle.net/1721.1/60315 https://orcid.org/0000-0002-7232-304X |
| _version_ | 1826209178558922752 |
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| author | Lauffenburger, Douglas A. Kamm, Roger Dale Genove, Elsa Borros, Salvador Semino, Carlos Eduardo Hernandez Vera, Rodrigo Alvarez, Lery |
| author2 | Massachusetts Institute of Technology. Center for Biomedical Engineering |
| author_facet | Massachusetts Institute of Technology. Center for Biomedical Engineering Lauffenburger, Douglas A. Kamm, Roger Dale Genove, Elsa Borros, Salvador Semino, Carlos Eduardo Hernandez Vera, Rodrigo Alvarez, Lery |
| author_sort | Lauffenburger, Douglas A. |
| collection | MIT |
| description | Development of tissues in vitro with dimensions larger than 150 to 200μm requires the presence of a functional vascular network. Therefore, we have studied capillary morphogenesis under controlled biological and biophysical conditions with the aim of promoting vascular structures in tissue constructs. We and others have previously demonstrated that physiological values of interstitial fluid flow normal to an endothelial monolayer in combination with vascular endothelial growth factor play a critical role during capillary morphogenesis by promoting cell sprouting. In the present work, we studied the effect that a range of interstitial flow velocities (0–50μm/min) has in promoting the amount, length, and branching of developing sprouts during capillary morphogenesis. The number of capillary-like structures developed from human umbilical vein endothelial cell monolayers across the interstitial flow values tested was not significantly affected. Instead, the length and branching degree of the sprouts presented a significant maximum at flow velocities of 10 to 20μm/min. More-over, at these same flow values, the phosphorylation level of Src also showed its peak. We discovered that capillary morphogenesis is restricted to patches of Src-activated cells (phosphorylated Src (pSrc)) at the monolayer, suggesting that the transduction pathway in charge of sensing the mechanical stimulus induced by flow is promoting predetermined mechanically sensitive areas (pSrc) to undergo capillary morphogenesis. |
| first_indexed | 2024-09-23T14:18:44Z |
| format | Article |
| id | mit-1721.1/60315 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T14:18:44Z |
| publishDate | 2010 |
| publisher | Mary Ann Liebert, Inc. |
| record_format | dspace |
| spelling | mit-1721.1/603152022-09-29T08:35:17Z Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis Lauffenburger, Douglas A. Kamm, Roger Dale Genove, Elsa Borros, Salvador Semino, Carlos Eduardo Hernandez Vera, Rodrigo Alvarez, Lery Massachusetts Institute of Technology. Center for Biomedical Engineering Massachusetts Institute of Technology. Department of Biological Engineering Lauffenburger, Douglas A. Lauffenburger, Douglas A. Kamm, Roger Dale Genove, Elsa Borros, Salvador Semino, Carlos Eduardo Hernandez Vera, Rodrigo Alvarez, Lery Development of tissues in vitro with dimensions larger than 150 to 200μm requires the presence of a functional vascular network. Therefore, we have studied capillary morphogenesis under controlled biological and biophysical conditions with the aim of promoting vascular structures in tissue constructs. We and others have previously demonstrated that physiological values of interstitial fluid flow normal to an endothelial monolayer in combination with vascular endothelial growth factor play a critical role during capillary morphogenesis by promoting cell sprouting. In the present work, we studied the effect that a range of interstitial flow velocities (0–50μm/min) has in promoting the amount, length, and branching of developing sprouts during capillary morphogenesis. The number of capillary-like structures developed from human umbilical vein endothelial cell monolayers across the interstitial flow values tested was not significantly affected. Instead, the length and branching degree of the sprouts presented a significant maximum at flow velocities of 10 to 20μm/min. More-over, at these same flow values, the phosphorylation level of Src also showed its peak. We discovered that capillary morphogenesis is restricted to patches of Src-activated cells (phosphorylated Src (pSrc)) at the monolayer, suggesting that the transduction pathway in charge of sensing the mechanical stimulus induced by flow is promoting predetermined mechanically sensitive areas (pSrc) to undergo capillary morphogenesis. Charles Stark Draper Laboratory National Institutes of Health (U.S.) (grant 1-RO1-EB003805-01A1) Translational Centre for Regenerative Medicine (1098SF TRM) 2010-12-17T20:36:50Z 2010-12-17T20:36:50Z 2009-07 Article http://purl.org/eprint/type/JournalArticle 1937-3341 http://hdl.handle.net/1721.1/60315 Hernández Vera, Rodrigo et al. “Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis.” Tissue Engineering Part A 15.1 (2010): 175-185. © 2009 Mary Ann Liebert, Inc. https://orcid.org/0000-0002-7232-304X en_US http://www.liebertonline.com/doi/abs/10.1089/ten.tea.2007.0314 Tissue Engineering. Part A 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 Mary Ann Liebert, Inc. Prof. Lauffenburger |
| spellingShingle | Lauffenburger, Douglas A. Kamm, Roger Dale Genove, Elsa Borros, Salvador Semino, Carlos Eduardo Hernandez Vera, Rodrigo Alvarez, Lery Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis |
| title | Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis |
| title_full | Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis |
| title_fullStr | Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis |
| title_full_unstemmed | Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis |
| title_short | Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis |
| title_sort | interstitial fluid flow intensity modulates endothelial sprouting in restricted src activated cell clusters during capillary morphogenesis |
| url | http://hdl.handle.net/1721.1/60315 https://orcid.org/0000-0002-7232-304X |
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