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A Steering Model of Endothelial Sheet Migration Recapitulates Monolayer Integrity and Directed Collective Migration

A Steering Model of Endothelial Sheet Migration Recapitulates Monolayer Integrity and Directed... A Steering Model of Endothelial Sheet Migration Recapitulates Monolayer Integrity and Directed Collective Migration ▿ † Philip Vitorino * , ‡ , Mark Hammer ‡ , Jongmin Kim and Tobias Meyer * Chemical and Systems Biology, Bio-X Program, Stanford University, 318 Campus Drive, Stanford, California 94305-5439 ABSTRACT Cells in endothelial cell monolayers maintain a tight barrier between blood and tissue, but it is not well understood how endothelial cells move within monolayers, pass each other, migrate when stimulated with growth factor, and also retain monolayer integrity. Here, we develop a quantitative steering model based on functional classes of genes identified previously in a small interfering RNA (siRNA) screen to explain how cells locally coordinate their movement to maintain monolayer integrity and collectively migrate in response to growth factor. In the model, cells autonomously migrate within the monolayer and turn in response to mechanical cues resulting from adhesive, drag, repulsive, and directed steering interactions with neighboring cells. We show that lateral-drag steering explains the local coordination of cell movement and the maintenance of monolayer integrity by allowing closure of small lesions. We further demonstrate that directional steering of cells at monolayer boundaries, combined with adhesive steering of cells behind, can explain growth factor-triggered collective migration into open space. Together, this model provides a mechanistic explanation for the observed genetic modularity and a conceptual framework for how cells can dynamically maintain sheet integrity and undergo collective directed migration. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Molecular and Cellular Biology American Society For Microbiology

A Steering Model of Endothelial Sheet Migration Recapitulates Monolayer Integrity and Directed Collective Migration

A Steering Model of Endothelial Sheet Migration Recapitulates Monolayer Integrity and Directed Collective Migration

Molecular and Cellular Biology , Volume 31 (2): 342 – Jan 15, 2011

Abstract

A Steering Model of Endothelial Sheet Migration Recapitulates Monolayer Integrity and Directed Collective Migration ▿ † Philip Vitorino * , ‡ , Mark Hammer ‡ , Jongmin Kim and Tobias Meyer * Chemical and Systems Biology, Bio-X Program, Stanford University, 318 Campus Drive, Stanford, California 94305-5439 ABSTRACT Cells in endothelial cell monolayers maintain a tight barrier between blood and tissue, but it is not well understood how endothelial cells move within monolayers, pass each other, migrate when stimulated with growth factor, and also retain monolayer integrity. Here, we develop a quantitative steering model based on functional classes of genes identified previously in a small interfering RNA (siRNA) screen to explain how cells locally coordinate their movement to maintain monolayer integrity and collectively migrate in response to growth factor. In the model, cells autonomously migrate within the monolayer and turn in response to mechanical cues resulting from adhesive, drag, repulsive, and directed steering interactions with neighboring cells. We show that lateral-drag steering explains the local coordination of cell movement and the maintenance of monolayer integrity by allowing closure of small lesions. We further demonstrate that directional steering of cells at monolayer boundaries, combined with adhesive steering of cells behind, can explain growth factor-triggered collective migration into open space. Together, this model provides a mechanistic explanation for the observed genetic modularity and a conceptual framework for how cells can dynamically maintain sheet integrity and undergo collective directed migration.

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References (28)

Publisher
American Society For Microbiology
Copyright
Copyright © 2011 by the American society for Microbiology.
ISSN
0270-7306
eISSN
1098-5549
DOI
10.1128/MCB.00800-10
pmid
20974808
Publisher site
See Article on Publisher Site

Abstract

A Steering Model of Endothelial Sheet Migration Recapitulates Monolayer Integrity and Directed Collective Migration ▿ † Philip Vitorino * , ‡ , Mark Hammer ‡ , Jongmin Kim and Tobias Meyer * Chemical and Systems Biology, Bio-X Program, Stanford University, 318 Campus Drive, Stanford, California 94305-5439 ABSTRACT Cells in endothelial cell monolayers maintain a tight barrier between blood and tissue, but it is not well understood how endothelial cells move within monolayers, pass each other, migrate when stimulated with growth factor, and also retain monolayer integrity. Here, we develop a quantitative steering model based on functional classes of genes identified previously in a small interfering RNA (siRNA) screen to explain how cells locally coordinate their movement to maintain monolayer integrity and collectively migrate in response to growth factor. In the model, cells autonomously migrate within the monolayer and turn in response to mechanical cues resulting from adhesive, drag, repulsive, and directed steering interactions with neighboring cells. We show that lateral-drag steering explains the local coordination of cell movement and the maintenance of monolayer integrity by allowing closure of small lesions. We further demonstrate that directional steering of cells at monolayer boundaries, combined with adhesive steering of cells behind, can explain growth factor-triggered collective migration into open space. Together, this model provides a mechanistic explanation for the observed genetic modularity and a conceptual framework for how cells can dynamically maintain sheet integrity and undergo collective directed migration.

Journal

Molecular and Cellular BiologyAmerican Society For Microbiology

Published: Jan 15, 2011

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