The nucleus of endothelial cell as a sensor of blood flow direction
Summary Hemodynamic shear stresses cause endothelial cells (ECs) to polarize in the plane of the flow. Paradoxically, under strong shear flows, ECs disassemble their primary cilia, common sensors of shear, and thus must use an alternative mechanism of sensing the strength and direction of flow. In o...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
The Company of Biologists
2013-08-01
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| Series: | Biology Open |
| Subjects: | |
| Online Access: | http://bio.biologists.org/content/2/10/1007 |
| _version_ | 1818944010309337088 |
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| author | Eugene Tkachenko Edgar Gutierrez Semion K. Saikin Per Fogelstrand Chungho Kim Alex Groisman Mark H. Ginsberg |
| author_facet | Eugene Tkachenko Edgar Gutierrez Semion K. Saikin Per Fogelstrand Chungho Kim Alex Groisman Mark H. Ginsberg |
| author_sort | Eugene Tkachenko |
| collection | DOAJ |
| description | Summary
Hemodynamic shear stresses cause endothelial cells (ECs) to polarize in the plane of the flow. Paradoxically, under strong shear flows, ECs disassemble their primary cilia, common sensors of shear, and thus must use an alternative mechanism of sensing the strength and direction of flow. In our experiments in microfluidic perfusion chambers, confluent ECs developed planar cell polarity at a rate proportional to the shear stress. The location of Golgi apparatus and microtubule organizing center was biased to the upstream side of the nucleus, i.e. the ECs polarized against the flow. These in vitro results agreed with observations in murine blood vessels, where EC polarization against the flow was stronger in high flow arteries than in veins. Once established, flow-induced polarization persisted over long time intervals without external shear. Transient destabilization of acto-myosin cytoskeleton by inhibition of myosin II or depolymerization of actin promoted polarization of EC against the flow, indicating that an intact acto-myosin cytoskeleton resists flow-induced polarization. These results suggested that polarization was induced by mechanical displacement of EC nuclei downstream under the hydrodynamic drag. This hypothesis was confirmed by the observation that acute application of a large hydrodynamic force to ECs resulted in an immediate downstream displacement of nuclei and was sufficient to induce persistent polarization. Taken together, our data indicate that ECs can sense the direction and strength of blood flow through the hydrodynamic drag applied to their nuclei. |
| first_indexed | 2024-12-20T07:36:25Z |
| format | Article |
| id | doaj.art-9d18b97969174f8a9e1968dde94bfaf9 |
| institution | Directory Open Access Journal |
| issn | 2046-6390 |
| language | English |
| last_indexed | 2024-12-20T07:36:25Z |
| publishDate | 2013-08-01 |
| publisher | The Company of Biologists |
| record_format | Article |
| series | Biology Open |
| spelling | doaj.art-9d18b97969174f8a9e1968dde94bfaf92022-12-21T19:48:17ZengThe Company of BiologistsBiology Open2046-63902013-08-012101007101210.1242/bio.2013462220134622The nucleus of endothelial cell as a sensor of blood flow directionEugene Tkachenko0Edgar Gutierrez1Semion K. Saikin2Per Fogelstrand3Chungho Kim4Alex Groisman5Mark H. Ginsberg6 Department of Medicine, University of California-San Diego, La Jolla, CA 92093, USA Department of Physics, University of California-San Diego, La Jolla, CA 92093, USA Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA Department of Molecular and Clinical Medicine, Gothenburg University, SE-413 45 Gothenburg, Sweden Department of Medicine, University of California-San Diego, La Jolla, CA 92093, USA Department of Physics, University of California-San Diego, La Jolla, CA 92093, USA Department of Medicine, University of California-San Diego, La Jolla, CA 92093, USA Summary Hemodynamic shear stresses cause endothelial cells (ECs) to polarize in the plane of the flow. Paradoxically, under strong shear flows, ECs disassemble their primary cilia, common sensors of shear, and thus must use an alternative mechanism of sensing the strength and direction of flow. In our experiments in microfluidic perfusion chambers, confluent ECs developed planar cell polarity at a rate proportional to the shear stress. The location of Golgi apparatus and microtubule organizing center was biased to the upstream side of the nucleus, i.e. the ECs polarized against the flow. These in vitro results agreed with observations in murine blood vessels, where EC polarization against the flow was stronger in high flow arteries than in veins. Once established, flow-induced polarization persisted over long time intervals without external shear. Transient destabilization of acto-myosin cytoskeleton by inhibition of myosin II or depolymerization of actin promoted polarization of EC against the flow, indicating that an intact acto-myosin cytoskeleton resists flow-induced polarization. These results suggested that polarization was induced by mechanical displacement of EC nuclei downstream under the hydrodynamic drag. This hypothesis was confirmed by the observation that acute application of a large hydrodynamic force to ECs resulted in an immediate downstream displacement of nuclei and was sufficient to induce persistent polarization. Taken together, our data indicate that ECs can sense the direction and strength of blood flow through the hydrodynamic drag applied to their nuclei.http://bio.biologists.org/content/2/10/1007MechanotransductionPlanar cell polarityEndotheliumShear stressNucleus |
| spellingShingle | Eugene Tkachenko Edgar Gutierrez Semion K. Saikin Per Fogelstrand Chungho Kim Alex Groisman Mark H. Ginsberg The nucleus of endothelial cell as a sensor of blood flow direction Biology Open Mechanotransduction Planar cell polarity Endothelium Shear stress Nucleus |
| title | The nucleus of endothelial cell as a sensor of blood flow direction |
| title_full | The nucleus of endothelial cell as a sensor of blood flow direction |
| title_fullStr | The nucleus of endothelial cell as a sensor of blood flow direction |
| title_full_unstemmed | The nucleus of endothelial cell as a sensor of blood flow direction |
| title_short | The nucleus of endothelial cell as a sensor of blood flow direction |
| title_sort | nucleus of endothelial cell as a sensor of blood flow direction |
| topic | Mechanotransduction Planar cell polarity Endothelium Shear stress Nucleus |
| url | http://bio.biologists.org/content/2/10/1007 |
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