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Microfluidic Devices for Quantifying the Role of Soluble Gradients in Early Angiogenesis

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Mechanical and Chemical Signaling in Angiogenesis

Part of the book series: Studies in Mechanobiology, Tissue Engineering and Biomaterials ((SMTEB,volume 12))

Abstract

Early angiogenesis, as defined by endothelial polarization and directional sprouting, is regulated by gradients of soluble factors in addition to a multitude of other anisotropic cues including interstitial flow, insoluble gradients, and topography of the extracellular matrix (ECM). Adding to this complexity, other microenvironmental inputs, such as matrix density and rigidity, are known to modulate the extent to which vascular endothelial cells react to these anisotropic cues. Given this complexity, novel platforms are needed to decouple and systematically assess signals regulating early angiogenesis. To this end, we discuss a microfluidic device that achieves stable, matrix-independent soluble gradients via passive diffusion, which shields the culture chamber from shear-induced anisotropy. These devices enable direct time-lapse imaging of single cell and collective cell phenomena within both two-dimensional (2D) and three-dimensional (3D) cultures. These experimental platforms have been used to quantify the growth factor concentration requirements that induce endothelial cell chemotaxis, to identify previously unknown regulators of brain angiogenesis, to screen biomaterials for their angiogenic potential, and to investigate the navigational ability of nascent sprouts.

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Authors and Affiliations

  1. Department of Bioengineering, Stanford University, 476 Lomita Mall, McCullough Room 246, Stanford, CA, 94305-4045, USA

    Patrick Benitez

  2. Department of Materials Science and Engineering, Stanford University, 476 Lomita Mall, McCullough Room 246, Stanford, CA, 94305-4045, USA

    Sarah Heilshorn

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  1. Patrick Benitez
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  2. Sarah Heilshorn
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Correspondence to Sarah Heilshorn .

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  1. Department of Biomedical Engineering, Cornell Univesity, Ithaca, USA

    Cynthia A. Reinhart-King

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Benitez, P., Heilshorn, S. (2013). Microfluidic Devices for Quantifying the Role of Soluble Gradients in Early Angiogenesis. In: Reinhart-King, C. (eds) Mechanical and Chemical Signaling in Angiogenesis. Studies in Mechanobiology, Tissue Engineering and Biomaterials, vol 12. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30856-7_3

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  • DOI: https://doi.org/10.1007/978-3-642-30856-7_3

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