The formation of microvascular networks (MVNs) is influenced by many aspects of the microenvironment, including soluble and insoluble biochemical factors and the biophysical properties of the surrounding matrix. It has also become clear that a dynamic and reciprocal interaction between the matrix and cells influences cell behavior. In particular, local matrix remodeling may play a role in driving cellular behaviors, such as MVN formation. In order to explore the role of matrix remodeling, an in vitro model of MVN formation involving suspending human umbilical vein endothelial cells within collagen hydrogels was used. The resulting cell and matrix morphology were microscopically observed and quantitative metrics of MVN formation and collagen gathering were applied to the resulting images. The macroscopic compaction of collagen gels correlates with the extent of MVN formation in gels of different stiffness values, with compaction preceding elongation leading to MVN formation. Furthermore, the microscopic analysis of collagen between cells at early timepoints demonstrates the alignment and gathering of collagen between individual adjacent cells. The results presented are consistent with the hypothesis that endothelial cells need to gather and align collagen between them as an early step in MVN formation.
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July 2013
Research-Article
Microscopic Matrix Remodeling Precedes Endothelial Morphological Changes During Capillary Morphogenesis
Claire McLeod,
Claire McLeod
Franklin W. Olin College of Engineering,
Needham, MA 02492;
Department of Bioengineering,
Needham, MA 02492;
Department of Bioengineering,
University of Pennsylvania
,Philadelphia, PA 19014
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John Higgins,
John Higgins
Franklin W. Olin College of Engineering
,Needham, MA 02492
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Yekaterina Miroshnikova,
Yekaterina Miroshnikova
Franklin W. Olin College of Engineering,
Department of Surgery,
Center for Bioengineering and Tissue Regeneration,
Needham, MA 02492
;Department of Surgery,
Center for Bioengineering and Tissue Regeneration,
University of California
,San Francisco
,San Francisco, CA 94143
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Rachel Liu,
Rachel Liu
Franklin W. Olin College of Engineering,
Department of Bioengineering,
Needham, MA 02492
;Department of Bioengineering,
University of Pennsylvania
,Philadelphia, PA 19014
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Alisha L. Sarang-Sieminski
Alisha L. Sarang-Sieminski
Franklin W. Olin College of Engineering
,Needham, MA 02492
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Claire McLeod
Franklin W. Olin College of Engineering,
Needham, MA 02492;
Department of Bioengineering,
Needham, MA 02492;
Department of Bioengineering,
University of Pennsylvania
,Philadelphia, PA 19014
John Higgins
Franklin W. Olin College of Engineering
,Needham, MA 02492
Yekaterina Miroshnikova
Franklin W. Olin College of Engineering,
Department of Surgery,
Center for Bioengineering and Tissue Regeneration,
Needham, MA 02492
;Department of Surgery,
Center for Bioengineering and Tissue Regeneration,
University of California
,San Francisco
,San Francisco, CA 94143
Rachel Liu
Franklin W. Olin College of Engineering,
Department of Bioengineering,
Needham, MA 02492
;Department of Bioengineering,
University of Pennsylvania
,Philadelphia, PA 19014
Alisha L. Sarang-Sieminski
Franklin W. Olin College of Engineering
,Needham, MA 02492
Contributed by the Bioengineering Division of ASME for publication in the JOURNAL OF BIOMECHANICAL ENGINEERING. Manuscript received October 1, 2012; final manuscript received February 25, 2013; accepted manuscript posted March 8, 2013; published online June 11, 2013. Assoc. Editor: Edward Sander.
J Biomech Eng. Jul 2013, 135(7): 071002 (7 pages)
Published Online: June 11, 2013
Article history
Received:
October 1, 2012
Revision Received:
February 25, 2013
Accepted:
March 8, 2013
Citation
McLeod, C., Higgins, J., Miroshnikova, Y., Liu, R., Garrett, A., and Sarang-Sieminski, A. L. (June 11, 2013). "Microscopic Matrix Remodeling Precedes Endothelial Morphological Changes During Capillary Morphogenesis." ASME. J Biomech Eng. July 2013; 135(7): 071002. https://doi.org/10.1115/1.4023984
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