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Author Notes:

denis.tsygankov@bme.gatech.edu

D.T. designed the computational and experimental studies, analyzed imaging data, and wrote the paper.

O.C. performed the majority of experiments and wrote the paper.

A.Z. developed the model, performed simulations, and edited the paper; S.H. analyzed RNA-seq data; W.P. analyzed images of cell patterns and edited the paper; K.Y. performed AFM experiments and edited the paper; J.O. and V.A. assisted in AFM data acquisition; T.A.S. provided resources and supervision of AFM experiments.

We thank Adriana Beltran for the gift of lentiviral vectors carrying shRNAs against krit1, ccm2, and pdcd10.

We also thank Drs. Timothy C. Elston and Gary L. Johnson for their immense support, stimulating discussions, and the ideas regarding the design of this project.

We wish to acknowledge the core facilities at the Parker H. Petit Institute for Bioengineering and Bioscience at the Georgia Institute of Technology for the use of their shared equipment, services, and expertise.

The authors declare no competing interests.

Subject:

Research Funding:

This work was supported by the U.S. Army Research Office (ARO) grant W911NF-17-1-0395 to D.T. and by funds from the Marcus Foundation, The Georgia Research Alliance, and the Georgia Tech Foundation through their support of the Marcus Center for Therapeutic Cell Characterization and Manufacturing (MC3M) at Georgia Tech.

Keywords:

  • Biological Sciences
  • Biomechanics
  • Biophysics
  • Cell Biology

Biomechanics of Endothelial Tubule Formation Differentially Modulated by Cerebral Cavernous Malformation Proteins.

Tools:

Journal Title:

iScience

Volume:

Volume 9

Publisher:

, Pages 347-358

Type of Work:

Article | Final Publisher PDF

Abstract:

At early stages of organismal development, endothelial cells self-organize into complex networks subsequently giving rise to mature blood vessels. The compromised collective behavior of endothelial cells leads to the development of a number of vascular diseases, many of which can be life-threatening. Cerebral cavernous malformation is an example of vascular diseases caused by abnormal development of blood vessels in the brain. Despite numerous efforts to date, enlarged blood vessels (cavernomas) can be effectively treated only by risky and complex brain surgery. In this work, we use a comprehensive simulation model to dissect the mechanisms contributing to an emergent behavior of the multicellular system. By tightly integrating computational and experimental approaches we gain a systems-level understanding of the basic mechanisms of vascular tubule formation, its destabilization, and pharmacological rescue, which may facilitate the development of new strategies for manipulating collective endothelial cell behavior in the disease context.

Copyright information:

© 2018 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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