The nucleus of endothelial cell as a sensor of blood circulation path [Research Post]
- Eugene Tkachenko1,two,
- Edgar Gutierrez2,
- Semion K. Saikinthree,
- Per Fogelstrandfour,
- Chungho Kimone,
- Alex Groismantwo,* and
- Mark H. Ginsbergone,*
1Office of Drugs, College of California-San Diego, La Jolla, CA 92093, United states
twoSection of Physics, University of California-San Diego, La Jolla, CA 92093, United states of america
3Division of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, United states of america
4Division of Molecular and Scientific Medication, Gothenburg University, SE-413 45 Gothenburg, Sweden
- ↵*Authors for correspondence ( )
Hemodynamic shear stresses cause endothelial cells (ECs) to polarize in the airplane of the movement. Paradoxically, under sturdy
shear flows, ECs disassemble their major cilia, common sensors of shear, and therefore must use an alternative mechanism of sensing
the power and course of circulation. In our experiments in microfluidic perfusion chambers, confluent ECs designed planar
cell polarity at a fee proportional to the shear anxiety. The area of Golgi apparatus and microtubule arranging centre
was biased to the upstream facet of the nucleus, i.e. the ECs polarized against the movement. These in vitro results agreed with
observations in murine blood vessels, the place EC polarization from the movement was much better in high circulation arteries than in veins.
After established, stream-induced polarization persisted in excess of prolonged time intervals with out exterior shear. Transient destabilization
of acto-myosin cytoskeleton by inhibition of myosin II or depolymerization of actin promoted polarization of EC towards the
movement, indicating that an intact acto-myosin cytoskeleton resists stream-induced polarization. These final results advised that polarization
was induced by mechanical displacement of EC nuclei downstream under the hydrodynamic drag. This speculation was confirmed
by the observation that acute application of a big hydrodynamic pressure to ECs resulted in an fast downstream displacement
of nuclei and was enough to induce persistent polarization. Taken collectively, our info indicate that ECs can perception the course
and strength of blood movement by way of the hydrodynamic drag utilized to their nuclei.
- Received March 1, 2013.
- Approved July nine, 2013.
- © 2013. Released by The Organization of Biologists Ltd
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