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Topography of extracellular matrix mediates vascular morphogenesis and migration speeds in angiogenesis

Bauer, Amy L ; Jackson, Trachette L ; Jiang, Yi Czirók, András

PLoS computational biology, 2009-07, Vol.5 (7), p.e1000445-e1000445 [Periódico revisado por pares]

United States: Public Library of Science

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Título:
Topography of extracellular matrix mediates vascular morphogenesis and migration speeds in angiogenesis
Autor: Bauer, Amy L ; Jackson, Trachette L ; Jiang, Yi
Czirók, András
Assuntos: Angiogenesis ; Animals ; BASIC BIOLOGICAL SCIENCES ; Binding sites ; Biochemistry & Molecular Biology ; Cancer ; Cardiovascular Disorders/Vascular Biology ; Cell adhesion & migration ; Cell Adhesion - physiology ; Cell Biology/Cell Adhesion ; Cell Biology/Cell Growth and Division ; Cell Biology/Morphogenesis and Cell Biology ; Cell Movement - physiology ; Cell research ; Cellular biology ; Collagen ; Computational Biology/Systems Biology ; Computer Simulation ; Corneal Neovascularization - metabolism ; Developmental Biology/Morphogenesis and Cell Biology ; Experiments ; Extracellular Matrix - physiology ; Limbus Corneae - blood supply ; Mathematical & Computational Biology ; Mathematical models ; Mathematics ; MATHEMATICS AND COMPUTING ; Mechanical properties ; Models, Biological ; Morphogenesis ; Neoplasm Transplantation ; Neovascularization ; Neovascularization, Physiologic - physiology ; Proteins ; Rabbits ; Reproducibility of Results ; Signal Transduction ; Systems Biology - methods ; Vascular Endothelial Growth Factor A - metabolism ; Wound healing
É parte de: PLoS computational biology, 2009-07, Vol.5 (7), p.e1000445-e1000445
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
USDOE Office of Science (SC), Basic Energy Sciences (BES)
AC52-06NA25396
Conceived and designed the experiments: ALB. Performed the experiments: ALB. Analyzed the data: ALB TLJ YJ. Contributed reagents/materials/analysis tools: ALB. Wrote the paper: ALB.
Descrição: The extracellular matrix plays a critical role in orchestrating the events necessary for wound healing, muscle repair, morphogenesis, new blood vessel growth, and cancer invasion. In this study, we investigate the influence of extracellular matrix topography on the coordination of multi-cellular interactions in the context of angiogenesis. To do this, we validate our spatio-temporal mathematical model of angiogenesis against empirical data, and within this framework, we vary the density of the matrix fibers to simulate different tissue environments and to explore the possibility of manipulating the extracellular matrix to achieve pro- and anti-angiogenic effects. The model predicts specific ranges of matrix fiber densities that maximize sprout extension speed, induce branching, or interrupt normal angiogenesis, which are independently confirmed by experiment. We then explore matrix fiber alignment as a key factor contributing to peak sprout velocities and in mediating cell shape and orientation. We also quantify the effects of proteolytic matrix degradation by the tip cell on sprout velocity and demonstrate that degradation promotes sprout growth at high matrix densities, but has an inhibitory effect at lower densities. Our results are discussed in the context of ECM targeted pro- and anti-angiogenic therapies that can be tested empirically.
Editor: United States: Public Library of Science
Idioma: Inglês

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Topography of extracellular matrix mediates vascular morphogenesis and migration speeds in angiogenesis

Bauer, Amy L ; Jackson, Trachette L ; Jiang, Yi Czirók, András

United States: Public Library of Science

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